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Besin V, Humardani FM, Yulianti T, Putra SED, Triana R, Justyn M. The Apo gene's genetic variants: hidden role in Asian vascular risk. Neurogenetics 2024; 25:157-164. [PMID: 38625441 DOI: 10.1007/s10048-024-00757-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 04/05/2024] [Indexed: 04/17/2024]
Abstract
Vascular risk factors, including diabetes, hypertension, hyperlipidemia, and obesity, pose significant health threats with implications extending to neuropsychiatric disorders such as stroke and Alzheimer's disease. The Asian population, in particular, appears to be disproportionately affected due to unique genetic predispositions, as well as epigenetic factors such as dietary patterns and lifestyle habits. Existing management strategies often fall short of addressing these specific needs, leading to greater challenges in prevention and treatment. This review highlights a significant gap in our understanding of the impact of genetic screening in the early detection and tailored treatment of vascular risk factors among the Asian population. Apolipoprotein, a key player in cholesterol metabolism, is primarily associated with dyslipidemia, yet emerging evidence suggests its involvement in conditions such as diabetes, hypertension, and obesity. While genetic variants of vascular risk are ethnic-dependent, current evidence indicates that epigenetics also exhibits ethnic specificity. Understanding the interplay between Apolipoprotein and genetics, particularly within diverse ethnic backgrounds, has the potential to refine risk stratification and enhance precision in management. For Caucasian carrying the APOA5 rs662799 C variant, pharmacological interventions are recommended, as dietary interventions may not be sufficient. In contrast, for Asian populations with the same genetic variant, dietary modifications are initially advised. Should dyslipidemia persist, the consideration of pharmaceutical agents such as statins is recommended.
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Affiliation(s)
| | - Farizky Martriano Humardani
- Faculty of Medicine, Universitas Surabaya, Surabaya, Indonesia.
- Magister in Biomedical Science Program, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
- Bioinformatics Research Center, Indonesian Bioinformatics and Biomolecular, Malang, Indonesia.
| | - Trilis Yulianti
- Prodia Education and Research Institute, Jakarta, Indonesia
- Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | | | - Rina Triana
- Prodia Clinical Laboratories, Jakarta, Indonesia
| | - Matthew Justyn
- Faculty of Pharmacy, Universitas Padjajaran, Jatinangor, Indonesia
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Meena K, Misra A, Vikram N, Ali S, Upadhyay AD, Luthra K. Genetic polymorphism of fatty acid binding protein-2 in hyperlipidemic Asian Indians in North India. Am J Hum Biol 2023; 35:e23834. [PMID: 36382874 DOI: 10.1002/ajhb.23834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 10/31/2022] [Accepted: 11/01/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Fatty acid binding protein-2 (FABP-2) is involved in the metabolism of lipids in the intestine. FABP-2 Ala54Thr polymorphism involves a transition of G to A at codon 54 of FABP-2, resulting in an amino acid substitution Ala54 to Thr54 and is associated with elevated fasting triglycerides in some hyperlipidemic populations. In current genome builds and gene databases the variant of the Ala54Thr FABP-2 (rs 1 799 883) is annotated as c.163A>G (p. Thr55Ala). AIM AND OBJECTIVE The status of this polymorphism in hyperlipidemic Asian Indians from North India has not been investigated. This study was aimed to evaluate the distribution of the polymorphic variants of the Ala54Thr FABP-2 and their association with lipids in hyperlipidemic subjects. METHODS Ala54Thr FABP-2 polymorphism in both hyperlipidemic (n = 210) and normolipidemic (n = 342) subjects was assessed by PCR-RFLP. RESULTS Ala54Thr genotypes and alleles distribution did not differ between the hyperlipidemic and normolipidemic groups. The heterozygous genotype FABP-2 Ala/Thr was significantly associated with higher levels of triglycerides and very low-density lipoproteins as compared to the homozygous variant (Thr/Thr) genotype and the wild type homozygous (Ala/Ala) genotype. CONCLUSIONS The heterozygous genotype FABP-2 Ala54Thr is a risk factor for the development of hypertriglyceridemia and increased levels of VLDL-c in Asian Indians from North India.
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Affiliation(s)
- Kiran Meena
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Anoop Misra
- Fortis CDOC Hospital for Diabetes and Allied Sciences, New Delhi, India
| | - Naval Vikram
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Shakir Ali
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Ashish Datt Upadhyay
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Kalpana Luthra
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Mahadevan M, Bose M, Gawron KM, Blumberg R. Metabolic Syndrome and Chronic Disease Risk in South Asian Immigrants: A Review of Prevalence, Factors, and Interventions. Healthcare (Basel) 2023; 11:healthcare11050720. [PMID: 36900725 PMCID: PMC10000781 DOI: 10.3390/healthcare11050720] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/21/2023] [Accepted: 02/26/2023] [Indexed: 03/05/2023] Open
Abstract
South Asians (SAs) are among the fastest-growing ethnic groups in the U.S. Metabolic syndrome (MetS) is a condition that is characterized by multiple health factors that increase the risk for chronic diseases, such as cardiovascular disease (CVD) and diabetes. MetS prevalence among SA immigrants ranges from 27-47% in multiple cross-sectional studies using different diagnostic criteria, which is generally higher compared to other populations in the receiving country. Both genetic and environmental factors are attributed to this increased prevalence. Limited intervention studies have shown effective management of MetS conditions within the SA population. This review reports MetS prevalence in SAs residing in non-native countries, identifies contributing factors, and discusses ways to develop effective community-based strategies for health promotion targeting MetS among SA immigrants. There is a need for more consistently evaluated longitudinal studies to facilitate the development of directed public health policy and education to address chronic diseases in the SA immigrant community.
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Affiliation(s)
- Meena Mahadevan
- Department of Nutrition and Food Studies, Montclair State University, Montclair, NJ 07043, USA
- Correspondence: ; Tel.: +1-973-655-7574
| | - Mousumi Bose
- Department of Nutrition and Food Studies, Montclair State University, Montclair, NJ 07043, USA
| | | | - Renata Blumberg
- Department of Nutrition and Food Studies, Montclair State University, Montclair, NJ 07043, USA
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Rana S, Ali S, Wani HA, Mushtaq QD, Sharma S, Rehman MU. Metabolic syndrome and underlying genetic determinants-A systematic review. J Diabetes Metab Disord 2022; 21:1095-1104. [PMID: 35673448 PMCID: PMC9167205 DOI: 10.1007/s40200-022-01009-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 02/13/2022] [Indexed: 12/18/2022]
Abstract
The metabolic syndrome is a cluster of heritable and related traits which has been associated with a range of pathophysiological factors including dyslipidaemia, abdominal obesity, increased fasting plasma glucose (FPG) and hypertension. The documented genetic basis of the metabolic syndrome include several chromosomal positions, numerous candidate gene-associated polymorphisms, different genetic variants, which are linked to the syndrome either as a trait or entities mainly linked to metabolic process. Additionally, the latest findings related to the contribution of epigenetic mechanisms, microRNAs, sporadic variants, non-coding RNAs, and assessing the role of genes in molecular systems has enhanced our understanding of the syndrome. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Nonetheless, a common shared genetic cause has not been established to clarify the coexistence of their components and further investigation is required. While mostly neglected and rarely known, hereditary predisposition needs to be studied, including with the current defective phenotypic condition descriptions. Metabolic syndrome is a multi-faceted characteristic with abundant properties and the condition can arise from interactions between environmental variables such as physical inactivity, caloric obesity and genetic susceptibility. Although there is support for genetic determinants from family and twin research, there is still no recognised genomic DNA marker for genetic association and linkages with quite a long way off potential for clinical application. In the present review efforts have been made to through light on the various genetic determinants with large effects that underlie with the association of these traits to this syndrome. The heterogeneity and multifactorial heritability of MetS, however, has been a challenge towards understanding the factors underlying the association of these traits.
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Affiliation(s)
- Sanjeev Rana
- grid.440710.60000 0004 1756 649XHuman Genomics Research Group, Shri Mata Vaishno Devi University (SMVDU), Katra, J and K India
| | - Shafat Ali
- grid.412997.00000 0001 2294 5433Cytogenetics and Molecular Biology Laboratory, Centre of Research for Development, University of Kashmir, Srinagar, J and K India
| | - Hilal Ahmad Wani
- grid.412997.00000 0001 2294 5433Department of Biochemistry, Government Degree College Sumbal, Bandipora, J and K India
| | | | - Swarkar Sharma
- grid.440710.60000 0004 1756 649XHuman Genomics Research Group, School of Biotechnology, Shri Mata Vaishno Devi University (SMVDU), Katra, J and K India
| | - Muneeb U Rehman
- grid.56302.320000 0004 1773 5396College of Clinical Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Bhori M, Rastogi V, Tungare K, Marar T. A review on interplay between obesity, lipoprotein profile and nutrigenetics with selected candidate marker genes of type 2 diabetes mellitus. Mol Biol Rep 2021; 49:687-703. [PMID: 34669123 DOI: 10.1007/s11033-021-06837-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 10/12/2021] [Indexed: 12/06/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus, a rapidly growing epidemic, and its frequently related complications demand global attention. The two factors commonly attributed to the epidemic are genetic factors and environmental factors. Studies indicate that the genetic makeup at an individual level and the environmental aspects influence the occurrence of the disease. However, there is insufficiency in understanding the mechanisms through which the gene mutations and environmental components individually lead to T2DM. Also, discrepancies have often been noted in the association of gene variants and type 2 diabetes when the gene factor is examined as a sole attribute to the disease. STUDY In this review initially, we have focused on the proposed ways through which CAPN10, FABP2, GLUT2, TCF7L2, and ENPP1 variants lead to T2DM along with the inconsistencies observed in the gene-disease association. The article also emphasizes on obesity, lipoprotein profile, and nutrition as environmental factors and how they lead to T2DM. Finally, the main objective is explored, the environment-gene-disease association i.e. the influence of each environmental factor on the aforementioned specific gene-T2DM relationship to understand if the disease-causing capability of the gene variants is exacerbated by environmental influences. CONCLUSION We found that environmental factors may influence the gene-disease relationship. Reciprocally, the genetic factors may alter the environment-disease relationship. To precisely conclude that the two factors act synergistically to lead to T2DM, more attention has to be paid to the combined influence of the genetic variants and environmental factors on T2DM occurrence instead of studying the influence of the factors separately.
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Affiliation(s)
- Mustansir Bhori
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India
| | - Varuni Rastogi
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India
| | - Kanchanlata Tungare
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India.
| | - Thankamani Marar
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India
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Srinivasan R, Padmapriyadarsini C, Ramesh K, Sanjeeva G, Reddy D, Suresh E, Kumar R, Sathyamoorthy P, Swaminathan S, Shet A. APOC3 Gene Polymorphism and Antiretroviral Therapy-Induced Dyslipidemia in HIV-Infected Children. AIDS Res Hum Retroviruses 2021; 37:92-100. [PMID: 33115242 DOI: 10.1089/aid.2020.0082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Children exposed to antiretroviral therapy (ART) are at risk of developing metabolic complications. The association between gene polymorphisms and the development of dyslipidemia in children post ART initiation was studied. Children initiating first-line ART were followed for 2 years at the National Institute for Research in Tuberculosis (Chennai, India), and St. John's Medical College Hospital (Bangalore, India). Clinical examination and fasting serum lipid profiles were measured every 6 months. Participants were genotyped for the polymorphisms in the APOC3 gene (rs2854116; rs2854117, and rs5128). Changes in lipid levels from baseline to months 6, 12, and 24, and the difference between the various genotype variants were analyzed using a modified analysis of variance test. Study enrolled 393 ART-naive HIV-infected children (mean age: 7.6 ± 3 years, mean weight: 18 ± 6) of whom 289 (75%) were started on nevirapine (NVP)-based ART and the remaining 96 (25%) were started on efavirenz-based ART. Only children carrying the GG allele of rs5128 genotype showed a decrease in CD4% and serum triglycerides pre-ART. An increasing trend of total cholesterol, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol were seen at 6 months in both EFZ and NVP groups, which subsequently stabilized by 12 months irrespective of genotype variants. Genotype variants of APOC3 (rs2854116 and rs2854117 polymorphism) did not show significant changes in serum lipid levels after 24 months of ART, whereas rs5128 polymorphism with "G" allele showed an association with HDL-c levels when on NVP-based ART. Our results suggest that ART plays a major role in normalizing lipid levels in HIV-infected children and APOC3 polymorphisms may not play a significant role in ART-induced dyslipidemia.
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Affiliation(s)
| | | | | | - G.N. Sanjeeva
- Indira Gandhi Institute of Child Health, Bangalore, India
| | - Devarajulu Reddy
- ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - Elumalai Suresh
- Institute of Child Health and Children's Hospital, Chennai, India
| | - Ramesh Kumar
- ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | | | | | - Anita Shet
- St. Johns Research Institute, Bangalore, India
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da Silva AS, Carvalho TL, do Ó KP, da Nóbrega DN, Dos Santos Souza R, da Silva Lima VF, Farias ICC, de Mendonça Belmont TF, de Mendonça Cavalcanti MDS, de Barros Miranda-Filho D. Association of the polymorphisms of the genes APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) with lipodystrophy in people living with HIV on antiretroviral therapy: a systematic review. Mol Biol Rep 2020; 47:4779-4787. [PMID: 32323264 DOI: 10.1007/s11033-020-05441-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 04/06/2020] [Indexed: 12/30/2022]
Abstract
The aim of this study was to perform a systematic review to identify data reported in the literature concerning the association of APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) polymorphisms with lipodystrophy in people living with HIV (PLWHIV) on antirretroviral therapy. The research was conducted in six databases and the studies were selected in two steps. First, a search was undertaken in the following electronic databases: PubMed, Science Direct, Medline, World Wide Science, Directory of Open Access Journals, Scielo, Lilacs and Medcarib. The titles and abstracts of 24,859 articles were read to select those that match the elegibilty criteria. Five papers that addressed the association of HAART, lipodystrophy and polymorphisms were selected for the review. There was no association between the polymorphisms of the genes APOC3 and PPARG and lipodystrophy. Another study described an association between the variant allele (G) of HFE and protection concerning the development of lipoatrophy (0.02) when compared with the reference allele (C). On the other hand, the variant allele (T) of the ESR2 gene was associated with the development of lipoatrophy (p = 0.007) when compared with the reference allele (C). In addition, the genotype and the variant allele of the gene MMP1 (2G) were associated with lipodystrophy in PLWHIV on HAART (p = 0.0002 and p = 0.0008, respectively). Therefore, further studies with other populations, involving PLWHIV on HAART are necessary to better understand the role of genetic markers, which may be involved in a predisposition to lipodystrophy.
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Affiliation(s)
| | - Tatiana Lins Carvalho
- Hospital Universitário Oswaldo Cruz (HUOC), Universidade de Pernambuco (UPE), Recife, PE, Brazil
| | - Kleyton Palmeira do Ó
- Instituto de Pesquisa Aggeu Magalhães (CPqAM), Fundação Oswaldo Cruz (FIOCRUZ), Recife, PE, Brazil
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Saki S, Saki N, Poustchi H, Malekzadeh R. Assessment of Genetic Aspects of Non-alcoholic Fatty Liver and Premature Cardiovascular Events. Middle East J Dig Dis 2020; 12:65-88. [PMID: 32626560 PMCID: PMC7320986 DOI: 10.34172/mejdd.2020.166] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Recent evidence has demonstrated a strong interplay and multifaceted relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). CVD is the major cause of death in patients with NAFLD. NAFLD also has strong associations with diabetes and metabolic syndrome. In this comprehensive review, we aimed to overview the primary environmental and genetic risk factors of NAFLD, and CVD and also focus on the genetic aspects of these two disorders. NAFLD and CVD are both heterogeneous diseases with common genetic and molecular pathways. We have searched for the latest published articles regarding this matter and tried to provide an overview of recent insights into the genetic aspects of NAFLD and CVD. The common genetic and molecular pathways involved in NAFLD and CVD are insulin resistance (IR), subclinical inflammation, oxidative stress, and atherogenic dyslipidemia. According to an investigation, the exact associations between genomic characteristics of NAFLD and CVD and casual relationships are not fully determined. Different gene polymorphisms have been identified as the genetic components of the NAFLDCVD association. Some of the most documented ones of these gene polymorphisms are patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), adiponectin-encoding gene (ADIPOQ), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), leptin receptor (LEPR), sterol regulatory element-binding proteins (SREBP), tumor necrosis factor-alpha (TNF-α), microsomal triglyceride transfer protein (MTTP), manganese superoxide dismutase (MnSOD), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), and mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain. Further cohort studies with a significant sample size using advanced genomic assessments and next-generation sequencing techniques are needed to shed more light on genetic associations between NAFLD and CVD.
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Affiliation(s)
- Sara Saki
- Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Saki
- Hoveizeh Cohort Study, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Poustchi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Danford CJ, Yao ZM, Jiang ZG. Non-alcoholic fatty liver disease: a narrative review of genetics. J Biomed Res 2018; 32:389-400. [PMID: 30355853 PMCID: PMC6283828 DOI: 10.7555/jbr.32.20180045] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver diseases worldwide. It encompasses a spectrum of disorders ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. One of the key challenges in NAFLD is identifying which patients will progress. Epidemiological and genetic studies indicate a strong pattern of heritability that may explain some of the variability in NAFLD phenotype and risk of progression. To date, at least three common genetic variants in the PNPLA3, TM6SF2, and GCKR genes have been robustly linked to NAFLD in the population. The function of these genes revealed novel pathways implicated in both the development and progression of NAFLD. In addition, candidate genes previously implicated in NAFLD pathogenesis have also been identified as determinants or modulators of NAFLD phenotype including genes involved in hepatocellular lipid handling, insulin resistance, inflammation, and fibrogenesis. This article will review the current understanding of the genetics underpinning the development of hepatic steatosis and the progression of NASH. These newly acquired insights may transform our strategy to risk-stratify patients with NAFLD and to identify new potential therapeutic targets.
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Affiliation(s)
- Christopher J Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
| | - Ze-Min Yao
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
| | - Z Gordon Jiang
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
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Maistry T, Gordon M, Sartorius B, Naidoo DP. Candidate gene polymorphisms related to lipid metabolism in Asian Indians living in Durban, South Africa. Indian J Med Res 2018; 148:169-179. [PMID: 30381540 PMCID: PMC6206769 DOI: 10.4103/ijmr.ijmr_1150_16] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND & OBJECTIVES Asian Indians have been shown to have a high prevalence of metabolic syndrome (MetS), related to insulin resistance and possibly genetic factors. The aim of this study was to determine the genetic patterns associated with MetS in Asian Indians living in Durban, South Africa. METHODS Nine hundred and ninety nine participants from the Phoenix Lifestyle Project underwent clinical, biochemical and genetic assessment. MetS was diagnosed according to the harmonized definition. The apolipoprotein A5 Q139X, lipoprotein lipase (LPL) Hinf I, human paraoxonase 1 (PON1) 192Arg/Gln, cholesteryl ester transfer protein (CETP) Taq1B, adiponectin 45T>G and leptin (LEP) 25CAG were genotyped by real-time polymerase chain reaction in participants with and without MetS. Univariate-unadjusted and multivariate-adjusted relations were conducted for all analyses. RESULTS The prevalence of MetS was high (49.0%). More females had MetS than males (51.0 vs 42.8%). There was no significant difference in the distribution of genotypes between participants with MetS and those without. Males with the MetS who had the adiponectin TG genotype and human paraoxonase 1 AA genotype were more likely to have reduced high-density lipoprotein cholesterol (HDL-C) (P=0.001) and higher systolic blood pressure (P=0.018), respectively. INTERPRETATION & CONCLUSIONS About half of the Asian Indians living in Phoenix had MetS. No association between the polymorphisms studied and the risk for MetS was observed. The adiponectin TG genotype may be associated with reduced HDL-C and the human paraoxonase 1 AA genotype with hypertension in males. This suggested that lifestyle factors were the major determinant for MetS in this ethnic group and the genetic risk might be related to its component risk factors than to MetS as an entity.
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Affiliation(s)
- Tanya Maistry
- Department of Cardiology, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
| | - Michelle Gordon
- Department of Molecular Biology, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
| | - Benn Sartorius
- Department of Public Health Medicine, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
| | - Datshana P. Naidoo
- Department of Cardiology, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
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Abstract
PURPOSE OF REVIEW We comment on the high prevalence of cardiovascular disease (CVD) in South Asians (SA). The effect of various risk factors, for example biochemical, genetic, lifestyle, socioeconomic factors and psychosocial stress on CVD risk is discussed. RECENT FINDINGS 'Prediabetes' is common in SA, but its relationship with coronary artery disease (CAD) is not significant unlike for the white population. At the same time, 'prediabetes' in SA is associated with an increased risk for cerebrovascular disease (CeVD). The differentiating factor could be the high lipids in Europeans and their relationship to CAD. Likewise, higher diastolic blood pressure in SA may explain the risk of CeVD. Small, dense, low-density lipoprotein (LDL), low high-density lipoprotein-cholesterol (HDL-C) concentration and high triglycerides may contribute to atherosclerosis. Thrombotic factors such as increased levels of plasminogen activator inhibitor, fibrinogen, lipoprotein (a) and homocysteine have been shown to be associated with increased CVD. Impaired cerebrovascular autoregulation and sympathovagal activity, increased arterial stiffness and endothelial dysfunction may increase CVD risk further. In addition, environmental and dietary factors may exaggerate the unfavourable cardiovascular profile through genetic factors. SUMMARY The implications of the findings suggest comprehensive screening of SA for CVD. Cultural differences should be considered while designing prevention strategies specifically targeting barriers for uptake of preventive service.
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Padmapriyadarsini C, Ramesh K, Sekar L, Ramachandran G, Reddy D, Narendran G, Sekar S, Chandrasekar C, Anbarasu D, Wanke C, Swaminathan S. Factors affecting high-density lipoprotein cholesterol in HIV-infected patients on nevirapine-based antiretroviral therapy. Indian J Med Res 2018; 145:641-650. [PMID: 28948955 PMCID: PMC5644299 DOI: 10.4103/ijmr.ijmr_1611_15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background & objectives: Cardiovascular disease (CVD) risk with low high-density lipoprotein cholesterol (HDL-C) and high triglycerides is common in the general population in India. As nevirapine (NVP)-based antiretroviral therapy (ART) tends to increase HDL-C, gene polymorphisms associated with HDL-C metabolism in HIV-infected adults on stable NVP-based ART were studied. Methods: A cross-sectional study was conducted between January 2013 and July 2014 among adults receiving NVP-based ART for 12-15 months. Blood lipids were estimated and gene polymorphisms in apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genes were analyzed by real-time polymerase chain reaction. Framingham's 10-yr CVD risk score was estimated. Logistic regression was done to show factors related to low HDL-C levels. Results: Of the 300 patients included (mean age: 38.6±8.7 yr; mean CD4 count 449±210 cell/μl), total cholesterol (TC) >200 mg/dl was observed in 116 (39%) patients. Thirty nine per cent males and 47 per cent females had HDL-C levels below normal while 32 per cent males and 37 per cent females had TC/HDL ratio of 4.5 and 4.0, respectively. Body mass index [adjusted odds ratio (aOR)=1.70, 95% confidence interval (CI) 1.01-2.84, P=0.04] and viral load (aOR=3.39, 95% CI: 1.52-7.52, P=0.003) were negatively associated with serum HDL-C levels. The 10-yr risk score of developing CVD was 11-20 per cent in 3 per cent patients. Allelic variants of APOC3 showed a trend towards low HDL-C. Interpretation & conclusions: High-risk lipid profiles for atherosclerosis and cardiovascular disease were common among HIV-infected individuals, even after 12 months of NVP-based ART. Targeted interventions to address these factors should be recommended in the national ART programmes.
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Affiliation(s)
- C Padmapriyadarsini
- Department of Clinical Research, ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - K Ramesh
- Department of Clinical Research, ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - L Sekar
- Department of Clinical Research, ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - Geetha Ramachandran
- Department of Clinical Research, ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - Devaraj Reddy
- Department of Clinical Research, ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - G Narendran
- Department of Clinical Research, ICMR-National Institute for Research in Tuberculosis, Chennai, India
| | - S Sekar
- ART Centre, Rajiv Gandhi Government General Hospital, Chennai, India
| | - C Chandrasekar
- Nodal ART Medical Officer, Government Hospital of Thoracic Medicine, Chennai, India
| | - D Anbarasu
- ART Centre, Government Vellore Medical College & Hospital, Vellore, India
| | - Christine Wanke
- Department of Medicine, Tufts University School of Medicine, Boston, USA
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13
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Synergic effects of the ApoC3 and ApoA4 polymorphisms on the risk of hypertension. Genes Genomics 2017. [DOI: 10.1007/s13258-017-0606-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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14
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Raza ST, Abbas S, Siddiqi Z, Mahdi F. Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2017; 6:121-130. [PMID: 28890888 PMCID: PMC5581553 DOI: 10.22088/acadpub.bums.6.2.6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 06/03/2017] [Indexed: 10/31/2022]
Abstract
Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.
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Affiliation(s)
- Syed Tasleem Raza
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow, India
| | - Shania Abbas
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow, India
| | - Zeba Siddiqi
- Department of Medicine Era's Lucknow Medical College and Hospital, Lucknow, India
| | - Farzana Mahdi
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow, India
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15
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Umano GR, Martino M, Santoro N. The Association between Pediatric NAFLD and Common Genetic Variants. CHILDREN-BASEL 2017. [PMID: 28629152 PMCID: PMC5483624 DOI: 10.3390/children4060049] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of obesity. Several studies have shown that genetic predisposition probably plays an important role in its pathogenesis. In fact, in the last few years a large number of genetic studies have provided compelling evidence that some gene variants, especially those in genes encoding proteins regulating lipid metabolism, are associated with intra-hepatic fat accumulation. Here we provide a comprehensive review of the gene variants that have affected the natural history of the disease.
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Affiliation(s)
- Giuseppina Rosaria Umano
- Department of Pediatrics, Yale University, 06520, New Haven, CT, USA.
- Dipartimento della Donna, del Bambino, di Vhirurgia Generale e Specialistica, Universita' della Campania Luigi Vanvitelli, 80138, Napoli, Italy.
| | - Mariangela Martino
- Department of Pediatrics, Yale University, 06520, New Haven, CT, USA.
- Dipartimento di Medicina V. Tiberio, Universita' del Molise, 86100, Campobasso, Italy.
| | - Nicola Santoro
- Department of Pediatrics, Yale University, 06520, New Haven, CT, USA.
- Dipartimento di Medicina V. Tiberio, Universita' del Molise, 86100, Campobasso, Italy.
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16
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Pemminati S, Millis RM, Kamath A, Shenoy AK, Gorantla VR. The Current Status of New Antidiabetic Drugs. J Pharmacopuncture 2016; 19:291-292. [PMID: 28070450 PMCID: PMC5217802 DOI: 10.3831/kpi.2016.19.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 09/06/2016] [Indexed: 11/09/2022] Open
Affiliation(s)
- Sudhakar Pemminati
- Department of Medical Pharmacology, American University of Antigua College of Medicine & Manipal University, St. John’s, Antigua and Barbuda
| | - Richard Mark Millis
- Department of Medical Physiology, American University of Antigua College of Medicine, St. John’s, Antigua and Barbuda
| | - Ashwin Kamath
- Department of Pharmacology, Kasturba Medical College, Manipal University, Mangalore, India
| | - Ashok Kudgi Shenoy
- Department of Pharmacology, Kasturba Medical College, Manipal University, Mangalore, India
| | - Vasavi Rakesh Gorantla
- Department of Behavioural Sciences and Neuroscience, AUA College of Medicine, St. John’s, Antigua and Barbuda
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17
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Gene Polymorphisms of FABP2, ADIPOQ and ANP and Risk of Hypertriglyceridemia and Metabolic Syndrome in Afro-Caribbeans. PLoS One 2016; 11:e0163421. [PMID: 27684940 PMCID: PMC5042446 DOI: 10.1371/journal.pone.0163421] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 09/08/2016] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES The metabolic syndrome (MetS) is a cluster of metabolic abnormalities and cardiovascular risk factors that are highly heritable and polygenic. We investigated the association of allelic variants of three candidate genes, rs1799883-FABP2, rs1501299-ADIPOQ and rs5065-ANP with MetS and its components, individually and in combination, using a genetic risk score. METHODS A cross-sectional study was conducted in 462 Afro-Caribbeans subjects without cardiovascular complications or lipid-lowering medications. Cardiovascular risk factors and MetS components (NCEP-ATPIII criteria) were recorded. The 3 SNPs were genotyped. The genetic risk score was calculated by summing the number of risk alleles at each locus. Logistic regressions were used. RESULTS Fifty-eight participants (12.6%) were diabetics and 116 (25.1%) had a MetS. In a dominant model, rs1799883 was associated with hypertriglyceridemia (OR 2.22; P = 0.014) and hypertriglyceridemic waist (HTGW), (P = 0.014) but not significantly with overweight (P = 0.049), abdominal obesity (P = 0.033) and MetS (P = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (P = 0.028) and 2.19 (P = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (P = 0.075). The genetic risk score was significantly associated with MetS. Subjects carrying 4-5 risk alleles (18.8%) had a nearly 2.5-fold-increased risk of MetS compared to those carrying 0-1 risk allele (24.3%): OR 2.31; P = 0.025. CONCLUSIONS This study supports the association of FABP2, ANP and ADIPOQ gene variants with MetS or its components in Afro-Caribbeans and suggests a cumulative genetic influence of theses variants on this syndrome and a potential effect on lipid metabolism.
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18
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Kim YR, Hong SH. Influences of −482C>T and 3238G>C polymorphisms of the Apolipoprotein C3 gene on prevalence of metabolic syndrome. Genes Genomics 2016. [DOI: 10.1007/s13258-016-0431-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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19
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Sookoian S, Pirola CJ. Review: Genetics of the cardiometabolic syndrome: new insights and therapeutic implications. Ther Adv Cardiovasc Dis 2016; 1:37-47. [DOI: 10.1177/1753944707082702] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Although the definition of the phenotype is imprecise, cardiometabolic syndrome (CMS) includes a constellation of complex diseases such as type 2 diabetes, dislipidemias, central obesity and hypertension, proinflammatory and prothrombotic states, ovarian polycystosis and fatty liver. The genetics of each disease is complex in itself and varies in spectrum from monogenic and syndromic models of inheritance, usually rare, to the most common polygenic and multifactorial forms. In addition, human studies using the candidate-gene approach indicate that common genetic variants of several genes are associated with the development of CMS. Genome-wide scans have also provided several chromosomal regions associated with some of the components of CMS. In addition, through comparative genomics animal models can generate a map for candidate loci in humans and a promising approach is offered by bioinformatic tools for gene prioritization. Lastly, the involvement of genes whose products are already the targets for approved drugs, such as SLC6A4, PPARα and PPARγ , in the development of CMS suggests new avenues for CMS pharmacological treatment.
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Affiliation(s)
- Silvia Sookoian
- Departamento de Sustancias Vasoactivas y Cardiología Molecular, Instituto de Investigaciones A Lanari, Universidad de Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina
| | - Carlos J. Pirola
- Departamento de Sustancias Vasoactivas y Cardiología Molecular, Instituto de Investigaciones A Lanari, Universidad de Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina, , pirola.carlos@lanari. fmed.uba.ar
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20
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Li XL, Sui JQ, Lu LL, Zhang NN, Xu X, Dong QY, Xin YN, Xuan SY. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review. Lipids Health Dis 2016; 15:53. [PMID: 26965314 PMCID: PMC4785616 DOI: 10.1186/s12944-016-0221-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 03/04/2016] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which represents a wide spectrum of hepatic damage. Several studies have reported that NAFLD is a strong independent risk factor for coronary artery disease (CAD). And patients with NAFLD are at higher risk and suggested undergoperiodic cardiovascular risk assessment. Cardiovascular disease (CVD) is responsible for the main cause of death in patients with NAFLD, and is mostly influenced by genetic factors. Both NAFLD and CAD are heterogeneous disease. Common pathways involved in the pathogenesis of NAFLD and CAD includes insulin resistance (IR), atherogenic dyslipidemia, subclinical inflammation, oxidative stress, etc. Genomic characteristics of these two diseases have been widely studied, further research about the association of these two diseases draws attention. The gene polymorphisms of adiponectin-encoding gene (ADIPOQ), leptin receptor (LEPR), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), sterol regulatory elementbinding proteins (SREBP), transmembrane 6 superfamily member 2 (TM6SF2), microsomal triglyceride transfer protein (MTTP), tumor necrosis factors-alpha (TNF-α) and manganese superoxide dismutase (MnSOD) have been reported to be related to NAFLD and CAD. In this review, we aimed to provide an overview of recent insights into the genetic basis of NAFLD and CAD.
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Affiliation(s)
- Xiao-Lin Li
- Department of Gastroenterology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, 266011, China
| | - Jian-Qing Sui
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, 266011, China
| | - Lin-Lin Lu
- Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.,Central Laboratories, Qingdao Municipal Hospital, Qingdao, 266071, China
| | - Nan-Nan Zhang
- Department of Gastroenterology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, 266011, China
| | - Xin Xu
- Department of Gastroenterology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, 266011, China
| | - Quan-Yong Dong
- Department of Gastroenterology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, 266011, China
| | - Yong-Ning Xin
- Department of Gastroenterology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, 266011, China. .,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, 266011, China. .,Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.
| | - Shi-Ying Xuan
- Department of Gastroenterology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, 266011, China. .,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, 266011, China. .,Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.
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21
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Abstract
The rising prevalence of diabetes in South Asians has significant health and economic implications. South Asians are predisposed to the development of diabetes due to biologic causes which are exacerbated by lifestyle and environmental factors. Furthermore, they experience significant morbidity and mortality from complications of diabetes, most notably coronary artery disease, cerebrovascular disease, and chronic kidney disease. Therefore, understanding the pathophysiology and genetics of diabetes risk factors and its associated complications in South Asians is paramount to curbing the diabetes epidemic. With this understanding, the appropriate screening, preventative and therapeutic strategies can be implemented and further developed. In this review, we discuss in detail the biologic and lifestyle factors that predispose South Asians to diabetes and review the epidemiology and pathophysiology of microvascular and macrovascular complications of diabetes in South Asians. We also review the ongoing and completed diabetes prevention and management studies in South Asians.
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22
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Qiu CJ, Ye XZ, Yu XJ, Peng XR, Li TH. Association between FABP2 Ala54Thr polymorphisms and type 2 diabetes mellitus risk: a HuGE Review and Meta-Analysis. J Cell Mol Med 2014; 18:2530-5. [PMID: 25388378 PMCID: PMC4302657 DOI: 10.1111/jcmm.12385] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 06/30/2014] [Indexed: 12/31/2022] Open
Abstract
Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta-analysis were performed. The PubMed and CNKI database was searched for case-control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild-type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04–1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05–1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta-analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians.
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Affiliation(s)
- Chun-Jian Qiu
- Department of Endocrinology, No. 81 Hospital of PLA, Nanjing, China
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23
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Apolipoprotein C3 gene polymorphisms in Southern Indian patients with nonalcoholic fatty liver disease. Indian J Gastroenterol 2014; 33:524-9. [PMID: 25319715 DOI: 10.1007/s12664-014-0504-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Accepted: 09/14/2014] [Indexed: 02/07/2023]
Abstract
AIM Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. A previous study has suggested an association of apolipoprotein C3 (APOC3) gene variants with the risk of NAFLD in Asian Indian men living in the Western regions. The present study was carried out with an aim to evaluate the association of demographic features, serum lipid profile and APOC3 gene variants (C-482T and T-455C) NAFLD. METHODS One hundred and fifty NAFLD patients and 150 age and gender-matched controls were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect the genotypes of APOC3. Serum lipid profile was analyzed. RESULTS In the present study, body mass index was not a predictive demographic marker for NAFLD. Serum triglycerides were higher in patients (mean 155.95 ± 59.0) with NAFLD compared to the control group (mean 133.75 ± 44.71) (p = 0.016). APOC3 gene polymorphism T-455C (rs2854116) was significantly associated with NAFLD (p = 0.001). However, we did not find a significant association of C-482T polymorphism (rs2854117) of APOC3 gene with NAFLD. Genotype -455C/C of the SNP, rs2854116 associated significantly with the elevated serum triglycerides in patients. CONCLUSIONS The polymorphism T-455C in APOC3 gene and elevated serum triglycerides were associated with NAFLD.
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24
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Abbas S, Raza ST, Chandra A, Rizvi S, Ahmed F, Eba A, Mahdi F. Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population. Ann Hum Biol 2014; 42:461-9. [DOI: 10.3109/03014460.2014.968206] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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25
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Li MR, Zhang SH, Chao K, Liao XH, Yao JY, Chen MH, Zhong BH. Apolipoprotein C3 (-455T>C) polymorphism confers susceptibility to nonalcoholic fatty liver disease in the Southern Han Chinese population. World J Gastroenterol 2014; 20:14010-14017. [PMID: 25320541 PMCID: PMC4194587 DOI: 10.3748/wjg.v20.i38.14010] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Revised: 04/18/2014] [Accepted: 05/29/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the relationship between Apolipoprotein C3 (APOC3) (-455T>C) polymorphism and nonalcoholic fatty liver disease (NAFLD) in the Southern Chinese Han population.
METHODS: In this prospective case-control study, we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese Han population at The First Affiliated Hospital, Sun Yat-sen University, from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3 (-455T>C) variants.
RESULTS: After adjusting for age, gender, and body-mass index, TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype, with adjusted odds ratios (ORs) of 1.77 (95%CI: 1.16-2.72) and 2.80 (95%CI: 1.64-4.79), respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance (IR) than those of the TT genotype, with an OR of 3.24 (95%CI: 1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL) (P < 0.05). No association was found between the APOC3 (-455T>C) polymorphism and obesity, impaired glucose tolerance, hyperuricemia, hypercholesterolemia, or high levels of low-density lipoprotein cholesterol (LDL) (P > 0.05).
CONCLUSION: APOC3 (-455T>C) genetic variation is involved in the susceptibility to developing NAFLD, IR, hypertension, hypertriglyceridemia, and low HDL in the Southern Chinese Han population.
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26
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Masebe T, Bessong PO, Ndip RN, Meyer D. Genetic variants of APOC3 promoter and HLA-B genes in an HIV infected cohort in northern South Africa: a pilot study. Int J Mol Sci 2014; 15:11403-15. [PMID: 24972136 PMCID: PMC4139789 DOI: 10.3390/ijms150711403] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 03/17/2014] [Accepted: 04/11/2014] [Indexed: 01/11/2023] Open
Abstract
Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of −482 (p = 1; χ2 = 0.00001) or −455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the −455C genotype, but not in males for the −455T genotype. Viral load decreases were significant with the −455C and −482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders.
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Affiliation(s)
- Tracy Masebe
- HIV/AIDS & Global Health Research Programme, Department of Microbiology, University of Venda, Thohoyandou 0950, South Africa.
| | - Pascal Obong Bessong
- HIV/AIDS & Global Health Research Programme, Department of Microbiology, University of Venda, Thohoyandou 0950, South Africa.
| | - Roland Ndip Ndip
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea Box 63, Cameroon.
| | - Debra Meyer
- Department of Biochemistry, University of Pretoria, Pretoria 0002, South Africa.
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27
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Aspiroz EL, Cabrera Figueroa SE, Cruz R, Porras Hurtado GL, Martín AF, Hurlé ADG, Carracedo A, Team TT. Toxicogenetics of lopinavir/ritonavir in HIV-infected European patients. Per Med 2014; 11:263-272. [PMID: 29764065 DOI: 10.2217/pme.14.7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
AIMS We present a genetic association study in 106 European HIV-infected individuals aimed at identifying and confirming polymorphisms that have a significant influence on toxicity derived from treatment with lopinavir/ritonavir (LPV/r). PATIENTS & METHODS Genotyping was performed by matrix-assisted laser desorption/ionization-time of flight and KASPar® (KBiosciences, Hoddesdon, UK); LPV/r plasma concentrations were quantified using HPLC with an UV detection system and the pharmacokinetic parameters were estimated using Bayesian algorithms. Genetic association analysis was performed with PASW Statistics 18 (SPSS Inc., IL, USA) and R for Windows (Microsoft, WA, USA). RESULTS Suggestive relationships have been established between lipid plasma levels and total bilirubin and SNPs in CETP, MCP1, ABCC2, LEP and SLCO1B3 genes and between diarrhea and SNPs in IL6 gene. CONCLUSION Replication analysis should confirm the novel results obtained in this study prior to its application in the clinical practice to achieve a safer LPV/r-based combined antiretroviral therapy.
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Affiliation(s)
| | - Salvador Enrique Cabrera Figueroa
- Pharmacy Service, University Hospital of Salamanca, Salamanca, Spain.,Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Raquel Cruz
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), University of Santiago de Compostela, Spain
| | - Gloria Liliana Porras Hurtado
- Fundación Pública Galega de Medicina Xenómica - Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS) - SERGAS (Servicio Galega de Saude), Santiago de Compostela, Spain.,Technological University of Pereira - Colciencias, Pereira, Colombia
| | | | | | - Angel Carracedo
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), University of Santiago de Compostela, Spain.,Fundación Pública Galega de Medicina Xenómica - Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS) - SERGAS (Servicio Galega de Saude), Santiago de Compostela, Spain.,Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - The Tormes Team
- Tormes Team, University Hospital of Salamanca, Salamanca, Spain
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28
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Alharbi KK, Khan IA, Bazzi MD, Al-Daghri NM, Hasan TN, Alnbaheen MS, Alharbi FK, Al-Sheikh YA, Syed R, Aboul-Soud MA. A54T polymorphism in the fatty acid binding protein 2 studies in a Saudi population with type 2 diabetes mellitus. Lipids Health Dis 2014; 13:61. [PMID: 24690233 PMCID: PMC4032166 DOI: 10.1186/1476-511x-13-61] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2014] [Accepted: 03/26/2014] [Indexed: 11/28/2022] Open
Abstract
Background Fatty acid-binding protein 2 (FABP2) is an intracellular protein expressed exclusively in the enterocytes of proximal small intestine. FABP2 has a high affinity for saturated and unsaturated long-chain fatty acids and is believed to be involved in the absorption and transport of dietary fatty acids. Methods This is a case–control study conceded in 438 T2DM cases and 460 subjects with normal glucose levels and non-obese considered as healthy controls. Allelic discrimination was performed using TaqMan single-nucleotide polymorphism was carried out by real time-polymerase chain reaction (RT-PCR) assays using purified DNA. Results Clinical data and anthropometric measurements except age, glucose levels and lipid profile of the patients were significantly different from those of the controls (p < 0.05). Statistical analyses failed to show any type of significant association of the polymorphism between cases and controls. However logistic regression analyses was suggests that the TT genotype is significantly associated with male patients (p = 0.001). None of the allele or genotypes of FABP2 A54T was associated with T2DM cases versus the controls (AT genotype, OR = 0.85 (0.64-1.12), p = 0.25; TT genotype, OR = 0.66 (0.39-1.11), p = 0.11; T allele, 0.82 (0.67-1.02), p = 0.08). Conclusion In conclusion, this study suggests that the above named variant in FABP2 gene is not potential contributor to the risk of T2DM and related traits in a Saudi population. However TT genotype is a risk factor for the disease in males.
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Affiliation(s)
| | - Imran Ali Khan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P,O, Box 10219, Riyadh 11433, Kingdom of Saudi Arabia.
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Swaminathan K, Mathavan A, Jebamani S. Diabetes and coronary artery disease in South Asians. ACTA ACUST UNITED AC 2013. [DOI: 10.1177/1474651413492177] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
South Asians originate from the Indian sub-continent and represent roughly one fifth of the world’s population. This ethnic group contributes to the highest proportion of coronary artery disease (CAD) burden, mainly attributed to the high prevalence of diabetes. However, other established and emerging risk factors are overrepresented in this population at a younger age. Further large scale research is needed to identify various genetic and environmental mechanisms underlying the increased diabetes and vascular risk in the South Asian population. Effective clinical strategies to reduce the risk of diabetes and CAD in the South Asian population are the need of the hour.
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Abstract
South Asia is home to one of the largest population of people with metabolic syndrome (MetS). The prevalence of MetS in South Asians varies according to region, extent of urbanization, lifestyle patterns, and socioeconomic/cultural factors. Recent data show that about one-third of the urban population in large cities in India has the MetS. All classical risk factors comprising the MetS are prevalent in Asian Indians residing in India. The higher risk in this ethnic population necessitated a lowering of the cut-off values of the risk factors to identify and intervene for the MetS to prevent diabetes and cardiovascular disease. Some pharmacological and nonpharmacological interventions are underway in MetS to assess the efficacy in preventing the diabetes and cardiovascular disease in this ethnic population.
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Affiliation(s)
- Kaushik Pandit
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Kolkata, India
| | - Soumik Goswami
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Kolkata, India
| | - Sujoy Ghosh
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Kolkata, India
| | - Pradip Mukhopadhyay
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Kolkata, India
| | - Subhankar Chowdhury
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Kolkata, India
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Wang H, Dong S, Xu H, Qian J, Yang J. Genetic variants in FTO associated with metabolic syndrome: a meta- and gene-based analysis. Mol Biol Rep 2011; 39:5691-8. [PMID: 22189543 DOI: 10.1007/s11033-011-1377-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2011] [Accepted: 12/13/2011] [Indexed: 01/19/2023]
Abstract
The objective of this study was to examine the effect of genetic variants in fat mass and obesity associated (FTO) gene on metabolic syndrome (MetS). A systematic literature search was performed and random-effects meta-analysis was used to evaluate genetic variants in FTO with MetS. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in FTO. A total of 18 studies from 13 published papers were included in our analysis. Random-effects meta-analysis yielded an estimated odds ratio of 1.19 (95% CI 1.12-1.27; P = 1.38 × 10(-7)) for rs9939609, 1.19 (95% CI 1.05-1.35; P = 0.008) for rs8050136, and 1.89 (95% CI 1.20-2.96; P = 0.006) for rs1421085. The gene-based analysis indicated that FTO is strongly associated with MetS (P < 10(-5)). This association remains after excluding rs9939609, a SNP that was frequently reported to have strong association with obesity and MetS. In this study, we concluded that the FTO gene may play a critical role in leading to MetS. Targeting this gene may provide novel therapeutic strategies for the prevention and treatment of metabolic syndrome.
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Affiliation(s)
- Haina Wang
- College of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China
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Abstract
Several candidate gene studies on the metabolic syndrome (MetS) have been conducted. However, for most single nucleotide polymorphisms (SNPs) no systematic review on their association with MetS exists. A systematic electronic literature search was conducted until the 2nd of June 2010, using HuGE Navigator. English language articles were selected. Only genes of which at least one SNP-MetS association was studied in an accumulative total population ≥ 4000 subjects were included. Meta-analyses were conducted on SNPs with three or more studies available in a generally healthy population. In total 88 studies on 25 genes were reviewed. Additionally, for nine SNPs in seven genes (GNB3, PPARG, TCF7L2, APOA5, APOC3, APOE, CETP) a meta-analysis was conducted. The minor allele of rs9939609 (FTO), rs7903146 (TCF7L2), C56G (APOA5), T1131C (APOA5), C482T (APOC3), C455T (APOC3) and 174G>C (IL6) were more prevalent in subjects with MetS, whereas the minor allele of Taq-1B (CETP) was less prevalent in subjects with the MetS. After having systematically reviewed the most studied SNP-MetS associations, we found evidence for an association with the MetS for eight SNPs, mostly located in genes involved in lipid metabolism.
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Affiliation(s)
- C M Povel
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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Coban N, Onat A, Guclu-Geyik F, Komurcu-Bayrak E, Sansoy V, Hergenc G, Can G, Erginel-Unaltuna N. Gender- and obesity-specific effect of apolipoprotein C3 gene (APOC3) -482C>T polymorphism on triglyceride concentration in Turkish adults. Clin Chem Lab Med 2011; 50:285-92. [PMID: 22004016 DOI: 10.1515/cclm.2011.747] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2011] [Accepted: 09/14/2011] [Indexed: 11/15/2022]
Abstract
BACKGROUND Apolipoprotein C3 (APOC3) gene polymorphisms are associated with cardiometabolic risk factors, varying in ethnicities. This study aimed to investigate such association between the APOC3 -482C>T polymorphism and cardiometabolic risk factors in the turkish adult risk factor (TARF) study cohort, stratifying by gender and obesity. METHODS Randomly selected 1548 individuals (757 male and 791 female, mean age 49.9±11.8 years) were genotyped for -482C>T polymorphism using hybridization probes in a Real-Time PCR LC480 device. RESULTS The -482TT genotype prevailed 9.9% in men and 11.5% in women. Association between 482C>T polymorphism and dyslipidemia (p=0.036, OR=1.42, 95%Cl=1.02-1.97) was found only in men. Analysis of variance showed that anthropometric and metabolic variables were not differently distributed in APOC3 -482C>T genotypes in the study population. In relation to dyslipidemia and obesity, the -482C>T polymorphism showed significant gender-by-genotype interactions (p<0.01). When the study population was stratified according to gender and obesity, homozygotes for the T allele were associated strongly with (by 45%) elevated fasting triglyceride concentrations in obese men (p=0.009) and homeostatic model assessment (HOMA) index in non-obese women (p=0.013). Furthermore, in the same subgroups, the associations of the fasting triglyceride concentrations and HOMA index with the TT genotype remained after adjustment for risk factors (p<0.05). CONCLUSIONS APOC3 -482TT genotype is independently associated with elevated fasting triglyceride concentrations in obese men. Presence of obesity seems to be required for this genotype to induce markedly elevated triglycerides. Furthermore, it is associated with the dyslipidemia in men, without requirement of obesity.
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Affiliation(s)
- Neslihan Coban
- Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Vakif Gureba Cad. Sehremini, Istanbul, Turkey
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Dodani S, Dong Y, Zhu H, George V. Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants? INDIAN JOURNAL OF HUMAN GENETICS 2011; 14:9-15. [PMID: 20300285 PMCID: PMC2840779 DOI: 10.4103/0971-6866.42321] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.
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Abstract
PURPOSE OF REVIEW Recent advancements in genotyping technology have contributed to an accelerated dissemination of information on sequence variation associated with hepatobiliary diseases and/or quantitative traits. RECENT FINDINGS Since the first genome-wide association study (GWAS) on genetic gallstone risk in 2007, a total of more than 25 GWAS related to the field have been reported. The identification of the IL-28B genotype as a critical host factor of natural and treatment-related outcomes in hepatitis C virus infection opens the avenue of personalized medicine and individual risk assessment by genetic information. By contrast, the second recent top-hit variant adiponutrin (PNPLA3) associated with liver fat content and fibrosis progression illustrates the potential of GWAS to identify novel pathobiological pathways. Another emerging research topic is in the designation of genetic markers for specific cirrhosis-related complications, such as spontaneous bacterial peritonitis (NOD2) and hepatic encephalopathy (glutaminase), of potential future relevance in prioritizing patients for preemptive treatment strategies. SUMMARY In this article we critically discuss new concepts in the genetics of hepatobiliary diseases with a special focus on the advantages and limitations of the GWAS approach. An update on relevant recent GWAS and selected candidate gene study data will be given.
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Affiliation(s)
- Vincent Zimmer
- Department of Medicine II, Saarland University Hospital, Homburg, Germany
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Zimmer V, Lammert F. Genetics and epigenetics in the fibrogenic evolution of chronic liver diseases. Best Pract Res Clin Gastroenterol 2011; 25:269-80. [PMID: 21497744 DOI: 10.1016/j.bpg.2011.02.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Accepted: 02/18/2011] [Indexed: 01/31/2023]
Abstract
Recent years have seen unprecedented progress in the identification and characterization of genetic information related to chronic liver diseases (CLDs). However, despite the conceptual benefit in early recognition of at-risk populations amenable to pre-emptive treatment and/or surveillance strategies, recent genomic research in the field has placed focus on unravelling the genetic architecture of disease susceptibility, while data on genetic markers anticipating an accelerated fibrogenesis in an individual are still limited. Likewise, sequence variation assigning rapid fibrogenic evolution common to CLDs irrespective of etiology are poorly defined aside from PNPLA3 (adiponutrin) as a prominent exception. The emerging field of epigenetics in hepatology has mostly been studied under the perspective of gene regulation, less so as a heritable alteration in gene activity. In this article we will critically discuss recent findings in genomic hepatology with special focus on the (epi)genetic contribution to the fibrogenic evolution of CLDs.
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Affiliation(s)
- Vincent Zimmer
- Department of Medicine II, Saarland University Hospital, Saarland University, Kirrberger Str., 66421 Homburg, Germany.
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Dodani S, Henkhaus R, Wick J, Vacek J, Gupta K, Dong L, Butler MG. Metabolic syndrome in South Asian immigrants: more than low HDL requiring aggressive management. Lipids Health Dis 2011; 10:45. [PMID: 21410987 PMCID: PMC3076254 DOI: 10.1186/1476-511x-10-45] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2011] [Accepted: 03/16/2011] [Indexed: 02/07/2023] Open
Abstract
Aggressive clinical and public health interventions have resulted in significant reduction in coronary artery disease (CAD) worldwide. However, South Asian immigrants (SAIs) exhibit the higher prevalence of CAD and its risk factors as compared with other ethnic populations. The objective of the current study is to assess the prevalence of metabolic syndrome (MS), its association with high density Lipoprotein (HDL) function, Apo lipoprotein A-I (APOA1) gene polymorphisms, and sub-clinical CAD using common carotid intima-media thickness (CCA-IMT) as a surrogate marker. A community-based cross-sectional study was conducted on SAIs aged 35-65 years. Dysfunctional/pro-inflammatory (Dys-HDL) was determined using novel cell free assay and HDL inflammatory index. Six intronic APOA1 gene polymorphisms were analyzed by DNA sequencing. According to the International Diabetes Federation definition, MS prevalence was 29.7% in SAIs without CAD and 26% had HDL inflammatory index ≥ 1 suggesting pro-inflammatory Dys-HDL. Six novel APOA1 single nucleotide polymorphisms (SNPs) were analyzed with logistic regression, three SNPs (G2, G3, and G5) were found to be significantly associated with MS (p = 0.039, p = 0.038, p = 0.054). On multi-variate analysis, MS was significantly associated with BMI > 23 (P = 0.005), Apo-A-I levels (p = 0.01), and Lp [a] (p < 0.0001). SAIs are known to be at a disproportionately high risk for CAD that may be attributed to a high burden for MS. There is need to explore and understand non-traditional risk factors with special focus on Dys-HDL, knowing that SAIs have low HDL levels. Large prospective studies are needed to further strengthen current study results.
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Affiliation(s)
- Sunita Dodani
- Center for Post Polio Rehabilitation, 2308 W. 127 street, Leawood, KS 66209, USA.
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Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology 2011; 53:467-74. [PMID: 21274868 PMCID: PMC3057507 DOI: 10.1002/hep.24072] [Citation(s) in RCA: 95] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2010] [Accepted: 11/03/2010] [Indexed: 12/22/2022]
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD) is an escalating health problem that is frequently associated with obesity and insulin resistance. The mechanistic relationship between NAFLD, obesity, and insulin resistance is not well understood. A nonsynonymous variant in patatin-like phospholipase domain containing 3 (rs738409, I148M) has been reproducibly associated with increased hepatic triglyceride content (HTGC) but has not been associated with either the body mass index (BMI) or indices of insulin resistance. Conversely, two sequence variants in apolipoprotein C3 (APOC3) that have been linked to hypertriglyceridemia (rs2854117 C > T and rs2854116 T > C) have recently been reported to be associated with both hepatic fat content and insulin resistance. Here we genotyped two APOC3 variants in 1228 African Americans, 843 European Americans and 426 Hispanics from a multiethnic population based study, the Dallas Heart Study and test for association with HTGC and homeostatic model of insulin resistance (HOMA-IR). We also examined the relationship between these two variants and HOMA-IR in the Atherosclerosis Risk in Communities (ARIC) study. No significant difference in hepatic fat content was found between carriers and noncarriers in the Dallas Heart Study. Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study; this lack of association was confirmed in the ARIC study, even after the analysis was restricted to lean (BMI < 25 kg/m(2) ) individuals (n = 4399). CONCLUSION Our data do not support a causal relationship between these two variants in APOC3 and either HTGC or insulin resistance in middle-aged men and women.
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Affiliation(s)
- Julia Kozlitina
- McDermott Center for Human Growth and Development, University of Texas Southwestern Medical CenterDallas, TX
| | - Eric Boerwinkle
- Human Genetics Center and Institute for Molecular Medicine, University of Texas Health Science CenterHouston, TX
| | - Jonathan C Cohen
- McDermott Center for Human Growth and Development, University of Texas Southwestern Medical CenterDallas, TX
| | - Helen H Hobbs
- McDermott Center for Human Growth and Development, University of Texas Southwestern Medical CenterDallas, TX,Howard Hughes Medical Institute, University of Texas Southwestern Medical CenterDallas, TX
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Comparison of BMI and anthropometric measures among South Asian Indians using standard and modified criteria. Public Health Nutr 2011; 14:809-16. [PMID: 21247513 DOI: 10.1017/s1368980010003307] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To compare the prevalence rates of obesity based on BMI/anthropometric measures, using WHO standard and ethnicity-specific criteria, the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF) definitions, among a migrant South Asian Indian population. DESIGN Cross-sectional study conducted in October 2007. SUBJECTS A total of 213 participants of South Asian descent over the age of 18 years. Measures included a questionnaire with basic demographic information and self-reported histories of diabetes, coronary artery disease and/or hypercholesterolaemia. Height, weight, waist and hip circumference and blood pressure measurements were obtained. SETTING Houston and surrounding suburbs. RESULTS WHO-modified (WHO-mod) BMI and IDF waist circumference (WC) criteria independently identified higher numbers of overweight/obese participants; however, when the WHO-mod BMI or IDF WC criteria were applied, nearly 75% of participants were categorized as overweight/obese--a proven risk factor for the future development of metabolic syndrome. CONCLUSIONS Obesity is likely under-diagnosed using the standard WHO and NCEP-ATPIII guidelines. Stressing the use of modified criteria more universally to classify obesity among South Asian Indians may be optimal to identify obesity and help appropriately risk stratify for intervention to prevent chronic diseases.
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Torres DM, Harrison SA. Nonalcoholic fatty liver disease: is it all in the genes? Hepatology 2010; 52:1851-4. [PMID: 21038421 DOI: 10.1002/hep.24020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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Krawczyk M, Bonfrate L, Portincasa P. Nonalcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 2010; 24:695-708. [PMID: 20955971 DOI: 10.1016/j.bpg.2010.08.005] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2010] [Accepted: 08/16/2010] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in the Western world, is a clinico-histopathological entity in which excessive triglyceride accumulation in the liver occurs. Non-alcoholic steatohepatitis (NASH) represents the necroinflammatory form, which can lead to advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of NAFLD/NASH is complex but increased visceral adiposity plus insulin resistance with increased free fatty acids release play an initial key role for the onset and perpetuation of liver steatosis. Further events in the liver include oxidative stress and lipid peroxidation, decreased antioxidant defences, early mitochondrial dysfunction, iron accumulation, unbalance of adipose-derived adipokines with a chronic proinflammatory status, and gut-derived microbial adducts. New gene polymorphisms increasing the risk of fatty liver, namely APOC3 and PNPLA3, have been lately identified allowing further insights into the pathogenesis of this condition. In our review pathophysiological, genetic, and essential diagnostic and therapeutic aspects of NAFLD are examined with future trends in this field highlighted.
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Affiliation(s)
- Marcin Krawczyk
- Department of Medicine II, Saarland University Hospital, Homburg, Germany
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Ruixing Y, Yiyang L, Meng L, Kela L, Xingjiang L, Lin Z, Wanying L, Jinzhen W, Dezhai Y, Weixiong L. Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels. Lipids Health Dis 2010; 9:86. [PMID: 20716347 PMCID: PMC2929234 DOI: 10.1186/1476-511x-9-86] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2010] [Accepted: 08/17/2010] [Indexed: 12/16/2022] Open
Abstract
Background Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Results Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. Conclusions This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG.
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Affiliation(s)
- Yin Ruixing
- Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, 22 Shuangyong Road, Nanning 530021, Guangxi, People's Republic of China.
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Zhao T, Nzekebaloudou M, lv J. Ala54Thr polymorphism of fatty acid-binding protein 2 gene and fasting blood lipids: A meta-analysis. Atherosclerosis 2010; 210:461-7. [DOI: 10.1016/j.atherosclerosis.2009.11.049] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2009] [Revised: 11/13/2009] [Accepted: 11/30/2009] [Indexed: 12/21/2022]
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Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM, Dziura J, Lifton RP, Shulman GI. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010; 362:1082-9. [PMID: 20335584 PMCID: PMC2976042 DOI: 10.1056/nejmoa0907295] [Citation(s) in RCA: 311] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease is associated with hepatic insulin resistance and type 2 diabetes mellitus. Whether this association has a genetic basis is unknown. METHODS In 95 healthy Asian Indian men, a group known to have a high prevalence of nonalcoholic fatty liver disease, we genotyped two single-nucleotide polymorphisms (SNPs) in the gene encoding apolipoprotein C3 (APOC3) that are known to be associated with hypertriglyceridemia (rs2854116 [T-455C] and rs2854117 [C-482T]). Plasma apolipoprotein C3 concentrations, insulin sensitivity, and hepatic triglyceride content were measured. We also measured plasma triglyceride concentrations and retinyl fatty acid ester absorption as well as plasma triglyceride clearance after oral and intravenous fat-tolerance tests. Liver triglyceride content and APOC3 genotypes were also assessed in a group of 163 healthy non-Asian Indian men. RESULTS Carriers of the APOC3 variant alleles (C-482T, T-455C, or both) had a 30% increase in the fasting plasma apolipoprotein C3 concentration, as compared with the wild-type homozygotes. They also had a 60% increase in the fasting plasma triglyceride concentration, an increase by a factor of approximately two in the plasma triglyceride and retinyl fatty acid ester concentrations after an oral fat-tolerance test, and a 46% reduction in plasma triglyceride clearance. The prevalence of nonalcoholic fatty liver disease was 38% among variant-allele carriers and 0% among wild-type homozygotes (P<0.001). The subjects with nonalcoholic fatty liver disease had marked insulin resistance. A validation study involving non-Asian Indian men confirmed the association between APOC3 variant alleles and nonalcoholic fatty liver disease. CONCLUSIONS The polymorphisms C-482T and T-455C in APOC3 are associated with nonalcoholic fatty liver disease and insulin resistance.
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Affiliation(s)
- Kitt Falk Petersen
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
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Yu J, Wang H, Yang S, Yuan J, Chen L, Chen CL, Huang DF, Wang Y, Ju SQ, Zhu J. The Effect of APOC3 Promoter Polymorphisms on the Risk of Hypertriglyceridemia in Chinese Han Population With or Without Type 2 Diabetes Mellitus. Lab Med 2010. [DOI: 10.1309/lmubypdivgqwoy2u] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Misra A, Khurana L. The Metabolic Syndrome in South Asians: Epidemiology, Determinants, and Prevention. Metab Syndr Relat Disord 2009; 7:497-514. [DOI: 10.1089/met.2009.0024] [Citation(s) in RCA: 218] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Affiliation(s)
- Anoop Misra
- Department of Diabetes and Metabolic Diseases, Fortis Hospital, Vasant Kunj, Delhi, India
- Center for Diabetes, Obesity, and Cholesterol Disorders (C-DOC), Diabetes Foundation (India), SDA, New Delhi, India
| | - Lokesh Khurana
- Center for Diabetes, Obesity, and Cholesterol Disorders (C-DOC), Diabetes Foundation (India), SDA, New Delhi, India
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Böhme M, Grallert H, Klapper M, Gieger C, Fischer A, Heid I, Wichmann HE, Döring F, Illig T. Association between functional FABP2 promoter haplotypes and body mass index: Analyses of 8072 participants of the KORA cohort study. Mol Nutr Food Res 2009; 53:681-5. [DOI: 10.1002/mnfr.200800225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Sandhofer A, Tatarczyk T, Laimer M, Ritsch A, Kaser S, Paulweber B, Ebenbichler CF, Patsch JR. The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome. Obesity (Silver Spring) 2008; 16:919-22. [PMID: 18239576 DOI: 10.1038/oby.2007.130] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The metabolic syndrome is associated with low high-density lipoprotein-cholesterol (HDL-C) and decreased low-density lipoprotein (LDL) particle size. The Taq1B-polymorphism in the cholesteryl ester-transfer protein (CETP)-gene influences HDL-C, CETP concentration, and LDL-size. We investigated the effect of the Taq1B-polymorphism on the risk of the metabolic syndrome in 1,503 participants (973 men, 530 women) of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n = 486) by an enzyme-linked immunosorbent assay. Prevalence of the metabolic syndrome was 16.7% (18.5% in men, 13.5% in women). The Taq1B-polymorphism influenced significantly CETP concentrations, HDL-C levels, and LDL-size (P < 0.001 for all). The relative risk of the metabolic syndrome was reduced by 32% (odds ratio (OR) 0.68 (95% CI: 0.51-0.89), P = 0.005) in carriers of the B2 variant. This risk reduction persisted after adjustment for age and sex (OR 0.69 (0.53-0.92), P = 0.01) and after further adjustment for body mass index, waist-to-hip ratio, blood pressure, insulin resistance (IR), HDL-C, and triglycerides (TGs) (OR 0.43 (0.26-0.72), P = 0.001). Furthermore, the risk reduction was more pronounced in men than in women. We conclude that CETP plays an important role in the metabolic syndrome, possibly involving novel functions of CETP.
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Affiliation(s)
- Anton Sandhofer
- Clinical Department of Internal Medicine, Clinical Division of General Internal Medicine, Medical University Innsbruck, Anichstrasse, Innsbruck, Austria.
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Dodani S. Excess coronary artery disease risk in South Asian immigrants: can dysfunctional high-density lipoprotein explain increased risk? Vasc Health Risk Manag 2008; 4:953-61. [PMID: 19183743 PMCID: PMC2605339 DOI: 10.2147/vhrm.s2915] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. DISCUSSION The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. CONCLUSIONS More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.
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