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Deng X, Tang K, Wang Z, He S, Luo Z. Impacts of Inflammatory Cytokines Variants on Systemic Inflammatory Profile and COVID-19 Severity. J Epidemiol Glob Health 2024; 14:363-378. [PMID: 38376765 PMCID: PMC11176143 DOI: 10.1007/s44197-024-00204-w] [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: 07/03/2023] [Accepted: 01/30/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. METHODS PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case-control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. RESULTS 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the -308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the -174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. CONCLUSIONS rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.
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Affiliation(s)
- XueJun Deng
- Department of Cardiology, Suining Central Hospital, Suining, 629000, Sichuan, China
| | - Kai Tang
- Department of Cardiology, Suining Central Hospital, Suining, 629000, Sichuan, China
| | - Zhiqiang Wang
- Orthopedic Center 1 Department of Orthopedic Trauma, Suining Central Hospital, Suining, Sichuan, China.
| | - Suyu He
- The Fourth Department of Digestive Disease Center, Suining Central Hospital, Suining, 629000, Sichuan, China.
| | - Zhi Luo
- Department of Cardiology, Suining Central Hospital, Suining, 629000, Sichuan, China.
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Shaswati M, Oeishy FH, Mumu SB, Zahid MZI, Hossain M, Haque MA, Reza HM, Mostaid MS. Polymorphisms of the interleukin-6 ( IL-6) gene contribute to cervical cancer susceptibility in Bangladeshi women: A case-control study. Health Sci Rep 2023; 6:e1238. [PMID: 37152226 PMCID: PMC10155201 DOI: 10.1002/hsr2.1238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 03/13/2023] [Accepted: 04/09/2023] [Indexed: 05/09/2023] Open
Abstract
Background and Aims Cervical cancer is characterized by abnormal cell growth in the lining of cervix and it is the second major cause of cancer-related deaths among females in Bangladesh. Interleukin-6 (IL-6) is a multifunctional cytokine that has been heavily linked with cervical cancer. Our aim was to investigate the association of two promoter single-nucleotide polymorphisms (SNPs) of IL-6 (rs1800795 and rs1800797) with the susceptibility of cervical cancer in Bangladeshi women. Methods DNA was extracted from venous blood samples from cervical cancer patients (n = 126) and healthy controls (n = 120). Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping of the selected SNPs. Logistic regression was performed to calculate the odds ratio (OR) with 95% confidence interval (CI) and p values. Results We found a significant association between rs1800795 and rs1800797 polymorphisms and cervical cancer. For, rs1800795 (G > C) the GC heterozygous genotype (OR = 2.80, 95% CI = 1.55-5.07, p = 0.0007) and CC mutant homozygous genotype (OR = 3.5, 95% CI = 1.29-9.51, p = 0.014) conferred an increased risk of cervical cancer. In case of rs1800797 (G > A) polymorphism, the AG heterozygous genotype (OR = 6.94, 95% CI = 3.76-12.81, p < 0.0001) and AA mutant homozygous genotype (OR = 3.88, 95% CI = 1.12-13.51, p = 0.0332) also exhibited an elevated risk of cervical cancer. Use of contraceptives was found as risk factor and patients who smoke were carriers of both the risk alleles and thus had an increased risk of cervical cancer. Conclusion Our findings suggest that polymorphism of rs1800795 and rs1800797 of the IL-6 gene play a significant role in cervical cancer susceptibility in Bangladeshi women.
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Affiliation(s)
- Monishita Shaswati
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
| | - Fihima Hossain Oeishy
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
| | - Sadia Biswas Mumu
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
| | - Md Zahidul Islam Zahid
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
| | - Murad Hossain
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
| | | | - Hasan Mahmud Reza
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
| | - Md Shaki Mostaid
- Department of Pharmaceutical Sciences, Faculty of Health and Life SciencesNorth South UniversityDhakaBangladesh
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Ugur MG, Kutlu R, Kilinc I. The effects of smoking on vascular endothelial growth factor and inflammation markers: A case-control study. CLINICAL RESPIRATORY JOURNAL 2018; 12:1912-1918. [DOI: 10.1111/crj.12755] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 11/29/2017] [Accepted: 12/02/2017] [Indexed: 11/30/2022]
Affiliation(s)
- Merve Guzeldulger Ugur
- Department of Family Medicine, Meram Medical Faculty; Necmettin Erbakan University; Konya Turkey
| | - Ruhusen Kutlu
- Department of Family Medicine, Meram Medical Faculty; Necmettin Erbakan University; Konya Turkey
| | - Ibrahim Kilinc
- Department of Medical Biochemistry, Meram Medicine Faculty; Necmettin Erbakan University; Konya Turkey
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Lajunen TK, Jaakkola JJK, Jaakkola MS. IL6 polymorphisms modify the effects of smoking on the risk of adult asthma. J Allergy Clin Immunol 2017; 141:799-802.e9. [PMID: 28987812 DOI: 10.1016/j.jaci.2017.09.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 09/08/2017] [Accepted: 09/18/2017] [Indexed: 01/23/2023]
Affiliation(s)
- Taina K Lajunen
- Center for Environmental and Respiratory Health Research (CERH), University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Jouni J K Jaakkola
- Center for Environmental and Respiratory Health Research (CERH), University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
| | - Maritta S Jaakkola
- Center for Environmental and Respiratory Health Research (CERH), University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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Abstract
Cigarette smoke contains more than 4500 chemicals which have toxic, mutagenic and carcinogenic effects. Strong evidences have shown that current smokers take a significantly higher risk of cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and lung cancer than nonsmokers. However, less attention has been paid to the smoking induced abnormalities in the individuals defined as healthy smokers who are normal with spirometry, radiographic images, routine physical exam and categorized as healthy control group in many researches. Actually, 'healthy smokers' are not healthy. This narrative review focuses on the smoking related pathophysiologic changes mainly in the respiratory system of healthy smokers, including inflammation and immune changes, genetic alterations, structural changes and pulmonary dysfunction.
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Affiliation(s)
- Zijing Zhou
- Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011 People’s Republic of China
| | - Ping Chen
- Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011 People’s Republic of China
| | - Hong Peng
- Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011 People’s Republic of China
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Gubina MA, Babenko VN, Ivanoshchuk DE, Shuryaeva AK, Latieva OO, Solov’eva IG, Ponomareva MN, Konovalova NA, Maksimov VN, Voevoda MI. Polymorphism of the c-fms, ITGB3, CCR2, and DBH genes in the populations of old believers of the Tyumen oblast and Russian residents of Novosibirsk. Mol Biol 2016. [DOI: 10.1134/s0026893316010052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Genetic variations underlying self-reported physical functioning: a review. Qual Life Res 2014; 24:1163-77. [PMID: 25387867 DOI: 10.1007/s11136-014-0844-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2014] [Indexed: 10/24/2022]
Abstract
PURPOSE Genetic associations with self-reported physical functioning (SPF) are less well-studied than genetic associations with performance-measured physical functioning (PPF). We review the literature on the associations of genetic variations on SPF. We provide an overview of SPF assessment, genetic contributions to SPF including heritability, effects of genetic variations and mutations, and effects of interventions on the gene-SPF relationship. We also aim to provide directions for future research. METHODS A computerized literature search using PubMed, Web of Science, and PsychInfo was conducted to select relevant literature published up to November 2013. Inclusion criteria were the use of an SPF questionnaire, original articles in English on human subjects, published in peer-reviewed journals and reporting significant associations between SPF and the genome. RESULTS Nineteen articles were included. SPF was commonly assessed with the Short Form-36 questionnaire involving mainly convenience samples of either older persons or chronically ill. Heritability estimates were 10-30 %. Candidate genes associated with SPF could be ascribed to biological pathways associated with neurodegeneration, physiological systems regulation, or cell regulation. The APOE gene associated with neurodegeneration was most studied (n = 3). Three papers included both SPF and PPF assessments. No genome-wide association study on SPF has been conducted. CONCLUSIONS Associations between SPF and the genome have been investigated in selected populations in a limited number of publications. Future research should consider increasing sample variation and incorporate both SPF and PPF assessments. Also, longitudinal studies should be conducted in order to elicit stronger conclusions regarding the genetic associations with SPF.
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Snyder EE, Walts B, Pérusse L, Chagnon YC, Weisnagel SJ, Rankinen T, Bouchard C. The Human Obesity Gene Map: The 2003 Update. ACTA ACUST UNITED AC 2012; 12:369-439. [PMID: 15044658 DOI: 10.1038/oby.2004.47] [Citation(s) in RCA: 207] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This is the tenth update of the human obesity gene map, incorporating published results up to the end of October 2003 and continuing the previous format. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome-wide scans and animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. Transgenic and knockout murine models relevant to obesity are also incorporated (N = 55). As of October 2003, 41 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. QTLs reported from animal models currently number 183. There are 208 human QTLs for obesity phenotypes from genome-wide scans and candidate regions in targeted studies. A total of 35 genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 272 studies reporting positive associations with 90 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. Overall, more than 430 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http://obesitygene.pbrc.edu.
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Affiliation(s)
- Eric E Snyder
- Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808-4124, USA
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Zhao N, Liu X, Wang Y, Liu X, Li J, Yu L, Ma L, Wang S, Zhang H, Liu L, Zhao J, Wang X. Association of inflammatory gene polymorphisms with ischemic stroke in a Chinese Han population. J Neuroinflammation 2012; 9:162. [PMID: 22769019 PMCID: PMC3464807 DOI: 10.1186/1742-2094-9-162] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Accepted: 07/06/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Inflammatory mechanisms are important in stroke risk, and genetic variations in components of the inflammatory response have been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in a Chinese Han population. METHODS A total of 1,124 ischemic stroke cases and 1,163 controls were genotyped with inflammatory panel strips containing 51 selected inflammatory gene polymorphisms from 35 candidate genes. We tested the genotype-stroke association with logistic regression model. RESULTS We found two single nucleotide polymorphisms (SNPs) in CCL11 were associated with ischemic stroke. After adjusting for multiple testing using false discovery rate (FDR) with a 0.20 cut-off point, CCL11 rs4795895 remained statistically significant. We further stratified the study population by their hypertension status. In the hypertensive group, CCR2 rs1799864, CCR5 rs1799987 and CCL11 rs4795895 were nominally associated with increased risk of stroke. In the non-hypertensive group, CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 and CCL11 rs4795895 were associated with ischemic stroke. After correction for multiple testing, CCR2 rs1799864 and CCR5 rs1799987 remained significant in the hypertensive group, and CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 remained significant in the non-hypertensive group. CONCLUSIONS Our results indicate that inflammatory genetic variants are associated with increased risk of ischemic stroke in a Chinese Han population, particularly in non-hypertensive individuals.
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Affiliation(s)
- Nan Zhao
- Department of Epidemiology, Public Health School, Harbin Medical University, Heilongjiang, China
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Eynon N, Ruiz JR, Meckel Y, Santiago C, Fiuza-Luces C, Gómez-Gallego F, Oliveira J, Lucia A. Is the −174 C/G polymorphism of theIL6gene associated with elite power performance? A replication study with two different Caucasian cohorts. Exp Physiol 2010; 96:156-62. [DOI: 10.1113/expphysiol.2010.055442] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Spasojević-Dimitrijeva B, Zivković M, Stanković A, Stojković L, Kostić M. The IL-6 -174G/C polymorphism and renal scarring in children with first acute pyelonephritis. Pediatr Nephrol 2010; 25:2099-106. [PMID: 20632037 DOI: 10.1007/s00467-010-1587-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2010] [Revised: 06/04/2010] [Accepted: 06/07/2010] [Indexed: 11/28/2022]
Abstract
Urinary tract infections (UTI) are common in infants and children and may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the new markers in relation to acute pyelonephritis (APN) and its treatment is essential for designing interventions that would minimize tissue damage. This prospective study investigated the first UTI infection in 71 children (age range: 1-24 months) in respect to interleukin-6 (IL-6) -174G/C polymorphism and renal scarring. The patients were divided into an APN group and a lower UTI group according to dimercaptosuccinic acid (DMSA). The IL-6 -174G/C genotypes were determined by tetra-primer ARMSPCR. Serum IL-6 was significantly higher in the APN group than in the group with lower UTI (p<0.05). In both groups, the -174G/C genotype and allele frequencies did not differ significantly from the control group. The highest white blood cell (WBC) count was observed in the CC genotype (p<0.05). A non-significant trend toward higher serum IL-6 was observed in children with CC genotype. On follow-up DMSA imaging performed 6 months later, renal scarring was detected in 36.9% of APN children. We did not find the significant association of IL-6 -174G/C polymorphism with APN and/or postinfectious renal scarring. These results indicate that serum IL-6 concentrations were significantly higher in children with APN than in patients with lower UTI.
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Ruiz JR, Buxens A, Artieda M, Arteta D, Santiago C, Rodríguez-Romo G, Lao JI, Gómez-Gallego F, Lucia A. The -174 G/C polymorphism of the IL6 gene is associated with elite power performance. J Sci Med Sport 2009; 13:549-53. [PMID: 19853505 DOI: 10.1016/j.jsams.2009.09.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2009] [Revised: 09/11/2009] [Accepted: 09/15/2009] [Indexed: 11/27/2022]
Abstract
The -174 G/C polymorphism [rs1800795] of the IL6 gene is a candidate to explain individual variations in health and exercise related phenotypes. We compared -174 G/C genotypic and allelic frequencies in three groups of men of the same Caucasian (Spanish) descent: elite endurance athletes (cyclists, runners; n=100); elite power athletes (jumpers, throwers, sprinters; n=53) and non-athletic controls (n=100). The frequency of the GG genotype (P=0.030) and G allele (P=0.026) was higher in the power athletes group compared with the control group. The frequency of the GG genotype (P=0.033) and G allele (P=0.013) was also higher in the power athletes group compared with the endurance athletes group. The odds ratio of being a power athlete if the subject had the GG genotype (dominant model) was 2.471 (95% confidence interval: 1.242-4.915) compared to the control group or the endurance athlete group. We did not find differences between the control and endurance athlete groups. In summary, our findings suggest that the G allele of the IL6 -174 G/C polymorphism might favour sprint/power sports performance.
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Affiliation(s)
- Jonatan R Ruiz
- Department of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden.
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Sunyer J, Forastiere F, Pekkanen J, Plana E, Kolz M, Pistelli R, Jacquemin B, Bruske-Hohlfeld I, Pitsavos C, Bellander T, Koenig W, Peters A. Interaction between smoking and the interleukin-6 gene affects systemic levels of inflammatory biomarkers. Nicotine Tob Res 2009; 11:1347-53. [DOI: 10.1093/ntr/ntp144] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Metrikat J, Albrecht M, Maya-Pelzer P, Ortlepp JR. Physical fitness is associated with lower inflammation, even in
individuals with high cholesterol – An alternative to statin
therapy? Glob Heart 2009. [DOI: 10.1016/j.cvdpc.2009.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Nassar BA, Nanji AA, Ransom TP, Rockwood K, Kirkland SA, MacPherson K, Connelly PW, Johnstone DE, O'Neill BJ, Bata IR, Andreou P, Title LM. Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk factors for early‐onset coronary artery disease in patients with no classic risk factors. Scandinavian Journal of Clinical and Laboratory Investigation 2009; 68:286-91. [DOI: 10.1080/00365510701697390] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Bray MS, Hagberg JM, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes: the 2006-2007 update. Med Sci Sports Exerc 2009; 41:35-73. [PMID: 19123262 DOI: 10.1249/mss.0b013e3181844179] [Citation(s) in RCA: 309] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
This update of the human gene map for physical performance and health-related fitness phenotypes covers the research advances reported in 2006 and 2007. The genes and markers with evidence of association or linkage with a performance or a fitness phenotype in sedentary or active people, in responses to acute exercise, or for training-induced adaptations are positioned on the map of all autosomes and sex chromosomes. Negative studies are reviewed, but a gene or a locus must be supported by at least one positive study before being inserted on the map. A brief discussion on the nature of the evidence and on what to look for in assessing human genetic studies of relevance to fitness and performance is offered in the introduction, followed by a review of all studies published in 2006 and 2007. The findings from these new studies are added to the appropriate tables that are designed to serve as the cumulative summary of all publications with positive genetic associations available to date for a given phenotype and study design. The fitness and performance map now includes 214 autosomal gene entries and quantitative trait loci plus seven others on the X chromosome. Moreover, there are 18 mitochondrial genes that have been shown to influence fitness and performance phenotypes. Thus,the map is growing in complexity. Although the map is exhaustive for currently published accounts of genes and exercise associations and linkages, there are undoubtedly many more gene-exercise interaction effects that have not even been considered thus far. Finally, it should be appreciated that most studies reported to date are based on small sample sizes and cannot therefore provide definitive evidence that DNA sequence variants in a given gene are reliably associated with human variation in fitness and performance traits.
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Affiliation(s)
- Molly S Bray
- USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA
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Aker S, Bantis C, Reis P, Kuhr N, Schwandt C, Grabensee B, Heering P, Ivens K. Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients. Nephrol Dial Transplant 2009; 24:2847-51. [PMID: 19349293 DOI: 10.1093/ndt/gfp141] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Inflammation is a well recognized central component of atherosclerotic processes in chronic kidney disease. Interleukin-6 (IL-6) levels are a strong determinant of cardiovascular mortality in dialysis patients. We evaluated the impact of IL-6 gene G-174C polymorphism associated with modified IL-6 production on the development of coronary artery disease (CAD), cardiovascular events and mortality in chronic dialysis patients. METHODS We studied n = 463 patients on chronic dialysis with angiographically confirmed (n = 218) or excluded (n = 245) CAD followed up for 65 months after initiation of dialysis. Monitored were arterial hypertension, diabetes mellitus, hyperlipidemia, smoking, CRP and fibrinogen. IL-6 gene G-174C polymorphism was determined by PCR amplification. RESULTS The CC genotype was associated with an impaired patient survival (p < 0.05) remaining an independent risk factor for death in multivariate analysis (HR for CC genotype: 3.58, CI: 1.41-9.07, p < 0.01). CC genotype carrying CAD patients suffered significant frequently cardiovascular events (revascularization, myocardial infarction, death) compared to GG/GC genotype carriers (85.2% vs. 66.5, p < 0.05). However, the IL-6 gene G-174C polymorphism was not related to the onset and development of CAD itself (ns) and the inflammation parameters CRP and fibrinogen did not differ between the genotypes under investigation (ns). CONCLUSIONS Our results suggest that IL-6 gene G-174C polymorphism is associated with the incidence of cardiovascular events and mortality in chronic dialysis patients.
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Affiliation(s)
- Sendogan Aker
- Department of Nephrology, Heinrich-Heine University, Germany.
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Molecular genetics of myocardial infarction. Genomic Med 2008; 2:7-22. [PMID: 18704761 DOI: 10.1007/s11568-008-9025-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2008] [Revised: 07/28/2008] [Accepted: 07/30/2008] [Indexed: 12/28/2022] Open
Abstract
Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The main causal and treatable risk factors for MI include hypertension, hypercholesterolemia or dyslipidemia, diabetes mellitus, and smoking. In addition to these risk factors, recent studies have shown the importance of genetic factors and interactions between multiple genes and environmental factors. Disease prevention is an important strategy for reducing the overall burden of MI, with the identification of markers for disease risk being key both for risk prediction and for potential intervention to lower the chance of future events. Although genetic linkage analyses of families and sib-pairs as well as candidate gene and genome-wide association studies have implicated several loci and candidate genes in predisposition to coronary heart disease (CHD) or MI, the genes that contribute to genetic susceptibility to these conditions remain to be identified definitively. In this review, we summarize both candidate loci for CHD or MI identified by linkage analyses and candidate genes examined by association studies. We also review in more detail studies that have revealed the association with MI or CHD of polymorphisms in MTHFR, LPL, and APOE by the candidate gene approach and those in LTA and at chromosomal region 9p21.3 by genome-wide scans. Such studies may provide insight into the function of implicated genes as well as into the role of genetic factors in the development of CHD and MI.
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Williams AG, Folland JP. Similarity of polygenic profiles limits the potential for elite human physical performance. J Physiol 2007; 586:113-21. [PMID: 17901117 PMCID: PMC2375556 DOI: 10.1113/jphysiol.2007.141887] [Citation(s) in RCA: 136] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Human physical capability is influenced by many environmental and genetic factors, and it is generally accepted that physical capability phenotypes are highly polygenic. However, the ways in which relevant polymorphisms combine to influence the physical capability of individuals and populations are unknown. Initially, the literature was searched to identify associations between 23 genetic polymorphisms and human endurance phenotypes. Next, typical genotype frequencies of those polymorphisms in the general population were obtained from suitable literature. Using probability calculations, we found only a 0.0005% chance of a single individual in the world having the 'preferable' form of all 23 polymorphisms. As the number of DNA variants shown to be associated with human endurance phenotypes continues to increase, the probability of any single individual possessing the 'preferable' form of each polymorphism will become even lower. However, with population turnover, the chance of such genetically gifted individuals existing increases. To examine the polygenic endurance potential of a human population, a 'total genotype score' (for the 23 polymorphisms) was calculated for each individual within a hypothetical population of 1000 000. There was considerable homogeneity in terms of genetic predisposition to high endurance potential, with 99% of people differing by no more than seven genotypes from the typical profile. Consequently, with population turnover world and Olympic records should improve even without further enhancement of environmental factors, as more 'advantageous' polygenic profiles occasionally, though rarely, emerge. More broadly, human potential appears limited by the similarity of polygenic profiles at both the 'elite sport' and 'chronic disorder' ends of the performance continuum.
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Affiliation(s)
- Alun G Williams
- Institute for Biophysical and Clinical Research into Human Movement, Manchester Metropolitan University, Hassall Road, Alsager, Cheshire, UK.
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Saijo Y, Yoshioka E, Fukui T, Kawaharada M, Sata F, Sato H, Kishi R. H pylori seropositivity and cytokine gene polymorphisms. World J Gastroenterol 2007; 13:4445-51. [PMID: 17724799 PMCID: PMC4611576 DOI: 10.3748/wjg.v13.i33.4445] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.
METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5´nuclease assay.
RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95%CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95%CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95%CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95%CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95%CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95%CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.
CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine polymorphisms and gene-environmental interactions on H pylori infection.
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Affiliation(s)
- Yasuaki Saijo
- Department of Health Science, Asahikawa Medical College, Midorigaoka, E2-1-1-1, Asahikawa, Hokkaido, Japan.
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Shin KK, Jang Y, Koh SJ, Chae JS, Kim OY, Park S, Choi D, Shin DJ, Kim HJ, Lee JH. Influence of the IL-6 -572C>G polymorphism on inflammatory markers according to cigarette smoking in Korean healthy men. Cytokine 2007; 39:116-22. [PMID: 17689974 DOI: 10.1016/j.cyto.2007.06.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2007] [Revised: 05/30/2007] [Accepted: 06/18/2007] [Indexed: 10/23/2022]
Abstract
We investigated whether smoking would interact with the interleukin-6 (IL-6) polymorphisms (-174G>C and -572C>G, -597G>A and -1363G>T) in determining circulating levels of inflammatory markers and its consequence to oxidative stress. The G/G genotype (n=26) of the -572C>G in nonsmokers (n=376) was associated with higher IL-6 (P=0.028), fibrinogen (P=0.007) and ox-LDL (P=0.006) than those with C/C (n=209) or C/G (n=141). Results were similar for nonsmokers and smokers (n=268), but in smokers, the -572G/G genotype was associated with a greater difference in levels of IL-6 (P=0.031), fibrinogen (P=0.001), ox-LDL (P=0.037) and PGF(2alpha) (P=0.050). IL-6 had positive relations with CRP, fibrinogen, ox-LDL and PGF(2alpha). There was no evidence of an effect of -572C>G genotype on CRP levels in nonsmokers, however, this polymorphism was associated with a highly significant effect on CRP in smokers (P<0.001) (genotype-smoking interaction P=0.04, adjusted for age, BMI and IL-6). The C allele frequency at the -174 promoter region of IL-6 was very rare (<0.01) and -597G>A and -1363G>T were monomorphic in this study. Our results suggest that IL-6 -572C>G has a greater response over time to the inflammatory effects of smoking and this may result in smokers having higher oxidative stress in subjects with G/G compared to C/C or C/G.
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Affiliation(s)
- Kyung-Kyun Shin
- Department of Family Medicine, College of Medicine, Pochon CHA University, Seoul, Republic of Korea
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Rankinen T, Bray MS, Hagberg JM, Pérusse L, Roth SM, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes: the 2005 update. Med Sci Sports Exerc 2007; 38:1863-88. [PMID: 17095919 DOI: 10.1249/01.mss.0000233789.01164.4f] [Citation(s) in RCA: 125] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The current review presents the 2005 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2005. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed, but a gene or locus must be supported by at least one positive study before being inserted on the map. By the end of 2000, in the early version of the gene map, 29 loci were depicted. In contrast, the 2005 human gene map for physical performance and health-related phenotypes includes 165 autosomal gene entries and QTL, plus five others on the X chromosome. Moreover, there are 17 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes. Thus, the map is growing in complexity. Unfortunately, progress is slow in the field of genetics of fitness and performance, primarily because the number of laboratories and scientists focused on the role of genes and sequence variations in exercise-related traits continues to be quite limited.
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Affiliation(s)
- Tuomo Rankinen
- Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808-4124, USA
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Saijo Y, Yoshioka E, Fukui T, Kawaharada M, Sata F, Sato H, Kishi R. Effects of the Interaction between Interleukin-6-634C/G Polymorphism and Smoking on Serum C-Reactive Protein Concentrations. Hypertens Res 2007; 30:593-9. [PMID: 17785926 DOI: 10.1291/hypres.30.593] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Smoking and interleukin-6 (IL-6) are major factors in inflammation. The aim of this study was to investigate whether or not the IL6 -634C/G polymorphism (rs1800796) and its interaction with smoking influence serum C-reactive protein (CRP) concentrations. The subjects were 347 Japanese male employees of a transit company. CRP and conventional cardiovascular risk factors were evaluated. IL6 -634C/G polymorphisms were genotyped by allelic discrimination using fluorogenic probes and the 5' nuclease assay. The mean values of CRP were significantly higher in current smokers than in nonsmokers after adjustment for age, body mass index (BMI), systolic blood pressure, total cholesterol, log triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting glucose, and drinking habit (p=0.011). Comparison of three genotypes revealed significant interaction between smoking and the IL6 -634C/G genotype manifested by CRP concentrations (p=0.007) after the adjustments cited above. After stratification by smoking status, CRP differed significantly among IL6 -634C/G genotypes groups in nonsmokers (p=0.010, p for trend=0.007), whereas no significant difference was found in current smokers. Comparison between -634C/C and C/G+G/G groups revealed also a significant interaction between smoking and the IL6 -634C/G genotype (p=0.007). These findings suggest that the impact of the -634G allele on CRP elevation is greater in nonsmokers than in current smokers. Since gene-environment interactions have been insufficiently examined, further studies are required to clarify their effect on inflammation, including CRP elevation.
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Affiliation(s)
- Yasuaki Saijo
- Department of Health Science, Asahikawa Medical College, Asahikawa, Japan.
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Fehrenbach E, Schneider ME. Trauma-induced systemic inflammatory response versus exercise-induced immunomodulatory effects. Sports Med 2006; 36:373-84. [PMID: 16646626 DOI: 10.2165/00007256-200636050-00001] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Accidental trauma and heavy endurance exercise, both induce a kind of systemic inflammatory response, also called systemic inflammatory response syndrome (SIRS). Exercise-related SIRS is conditioned by hyperthermia and concomitant heat shock responses, whereas trauma-induced SIRS manifests concomitantly with tissue necrosis and immune activation, secondarily followed by fever. Inflammatory cytokines are common denominators in both trauma and exercise, although there are marked quantitative differences. Different anti-inflammatory cytokines may be involved in the control of inflammation in trauma- and exercise-induced stress. Exercise leads to a balanced equilibrium between inflammatory and anti-inflammatory responses. Intermittent states of rest, as well as anti-oxidant capacity, are lacking or minor in trauma but are high in exercising individuals. Regular training may enhance immune competence, whereas trauma-induced SIRS often paves the way for infectious complications, such as sepsis.
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Affiliation(s)
- Elvira Fehrenbach
- Institute of Clinical and Experimental Transfusion Medicine, University of Tuebingen, Tuebingen, Germany.
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Jang Y, Koh SJ, Kim OY, Kim BK, Choi D, Hyun YJ, Kim HJ, Chae JS, Lee JH. Effect of the 252A>G polymorphism of the lymphotoxin-alpha gene on inflammatory markers of response to cigarette smoking in Korean healthy men. Clin Chim Acta 2006; 377:221-7. [PMID: 17113059 DOI: 10.1016/j.cca.2006.10.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2006] [Revised: 09/29/2006] [Accepted: 10/02/2006] [Indexed: 11/23/2022]
Abstract
BACKGROUND The systemic inflammatory response is heightened in smokers. We examined whether the established cardiovascular risk factor, smoking status, might interact with the lymphotoxin-alpha (LTA) gene 252A>G polymorphism in determining concentrations of TNF-alpha and eventually IL-6, adiponectin and CRP downstream in the inflammatory cascade. METHODS We measured anthropometric parameters, serum lipid profile, glucose, TNF-alpha, IL-6, CRP, adiponectin and urinary excretion of 8-epi PGF2alpha as well as a genotyping for 252A>G polymorphism of LTA in 480 healthy Korean men. RESULTS After adjustment for age, 208 smokers with an average consumption of 18+/-1 cigarettes/d had higher concentrations of TNF-alpha, IL-6, CRP and urinary excretion of 8-epi PGF2alpha than nonsmokers (n=272). Nonsmokers with G/G had higher TNF-alpha and 8-epi PGF2alpha concentrations than those with A/A or A/G. TNF-alpha concentrations were higher in smokers than nonsmokers of the same genotype. Smokers with G/G showed higher TNF-alpha concentration than those with A/A and had higher IL-6 and urinary 8-epi PGF2alpha concentrations than those with A/G or A/A. Furthermore, smokers carrying the G allele showed lower adiponectin concentrations than those with A/A. There are main effects of genotype and smoking, as well as the smoking-genotype interaction to TNF-alpha concentration. CONCLUSION Our results suggest that the LTA 252A>G polymorphism may modulate the inflammatory effects and oxidative stress of smoking. The detrimental effect of smoking is most clearly seen in men with G/G, suggesting a genotype-specific interaction with smoking.
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Affiliation(s)
- Yangsoo Jang
- Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, and Cardiovascular Center of National Health Insurance Corporation Ilsan Hospital, Koyang, Republic of Korea [corrected]
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Ortlepp JR, Graf J, Vesper K, Schmitz F, Mevissen V, Sucigan S, Kersten A, Weber C, Janssens U. Relationship of five inflammatory gene polymorphisms with morbidity and mortality in 533 patients admitted to an ICU. Inflammation 2006; 29:65-71. [PMID: 16858645 DOI: 10.1007/s10753-006-9000-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The aim of this study was to analyze the association of polymorphisms of five candidate genes with the outcome of consecutive patients admitted to a medical ICU. MATERIALS AND METHODS The study population was prospectively recruited. Inclusion criteria were admission to the ICU and written informed consent by the patients or their relatives. A total of 533 patients were recruited. The morbidity was assessed by SAPS II Score. Outcome data of in hospital mortality and length of ICU and hospital stay were obtained. Genotyping for genetic polymorphisms (CRP 1059, IL1B -511, CTGF -477, CCR2 64VI, IL6 -174) were performed by allele-specific fluorogenic oligonucleotide probes (TaqMan analysis). RESULTS All of the investigated polymorphisms were not associated with an altered outcome. There was no difference in morbidity and ICU or in-hospital mortality (neither in cross tabs analysis nor in Kaplan Meier or Cox regression analysis including age, gender and diagnosis as covariates) between the different genotypes. CONCLUSIONS Genotyping of the investigated polymorphism for risk stratification of patients admitted to ICU does not seem to be appropriated.
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Affiliation(s)
- Jan R Ortlepp
- Interdisciplinary Intermediate Care, University Hospital of Aachen-RTWTH, Pauwelsstrasse 30, 52057 Aachen, Germany
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Ortlepp JR, Krantz C, Kimmel M, von Korff A, Vesper K, Schmitz F, Mevissen V, Janssens U, Franke A, Hanrath P, Zerres K, Hoffmann R. Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years. Int J Cardiol 2006; 105:90-5. [PMID: 16207551 DOI: 10.1016/j.ijcard.2005.03.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2004] [Revised: 03/02/2005] [Accepted: 03/02/2005] [Indexed: 11/16/2022]
Abstract
BACKGROUND Cardiovascular risk factors (CRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined. METHODS Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus). RESULTS In patients <65 years (n=1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%CI 1.07-1.79, p=0.016 GC/CC: 1.28, 95%CI 1.03-1.60, p=0.028 VI/II: 1.49, 95%CI 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p<0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p<0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was the prevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p< 0.0001). Age was not associated with MI. In patients > or =65 years (n=1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI. CONCLUSION Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain.
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Affiliation(s)
- Jan R Ortlepp
- Medical Clinic I, University Hospital of Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
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Cermakova Z, Petrkova J, Arakelyan A, Drabek J, Mrazek F, Lukl J, Petrek M. The MCP-1 -2518 (A to G) single nucleotide polymorphism is not associated with myocardial infarction in the Czech population. Int J Immunogenet 2005; 32:315-8. [PMID: 16164699 DOI: 10.1111/j.1744-313x.2005.00530.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Monocyte chemoattractant protein (MCP)-1 is the key chemokine in the process of atheroslerotic vascular inflammation. Examining already reported association between coronary artery disease (CAD) and the SNP A/G in the MCP-1 gene (position -2518), 139 Czech patients with CAD manifested as myocardial infarction (MI) and 359 unrelated healthy control (C) subjects were genotyped by PCR-SSP. Genotype and allele frequencies were not different in MI and C groups (allele G: MI, 20.5%; C, 23.8%, OR = 0.8, P > 0.05). No differences were detected when the patients were subdivided based on sex or the age of MI first occurrence. Further, no relationship was observed between circulating MCP-1 levels and carriage of the G allele. The data do not support a role for the MCP-1 -2518 single nucleotide polymorphism in susceptibility to CAD manifested by myocardial infarction.
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Affiliation(s)
- Z Cermakova
- Immunology & Immunogenetics, Palacky University & Faculty Hospital Olomouc, Czech Republic
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Abstract
It has been recognized for some time that cardiovascular disease and type 2 diabetes are, to a major extent, inflammatory disorders associated with an environment characterized by a sedentary lifestyle together with abundant intakes of calories. Systemic low-level inflammation is suggested to be a cause as well as consequence of pathological processes with local tumor necrosis factor alpha production as an important biological driver. It is hypothesized that physical inactivity contributes to an enhanced proinflammatory burden independently of obesity, as regular muscle contractions mediate signals with myokines/cytokines as important messengers, which suppress proinflammatory activity at distant sites as well as within skeletal muscle. Muscle-derived interleukin (IL)-6 is considered to possess a central role in anti-inflammatory activities and health beneficial effects in relation to physical exercise. It is discussed how this fits the consistent observation that enhanced plasma levels of IL-6 represent a strong risk marker in chronic disorders associated with systemic low-level inflammation and all-cause mortality.
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Affiliation(s)
- Helle Bruunsgaard
- Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen East, Denmark.
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Petrkova J, Cermakova Z, Lukl J, Petrek M. CC chemokine receptor 5 (CCR5) deletion polymorphism does not protect Czech males against early myocardial infarction. J Intern Med 2005; 257:564-6. [PMID: 15910562 DOI: 10.1111/j.1365-2796.2005.01491.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Weger M, Steinbrugger I, Haas A, März W, El-Shabrawi Y, Weger W, Schmut O, Renner W. Role of the interleukin-6 -174 G>C gene polymorphism in retinal artery occlusion. Stroke 2004; 36:249-52. [PMID: 15604420 DOI: 10.1161/01.str.0000151329.84830.37] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE Proinflammatory cytokines including interleukin-6 (IL-6) are supposed to play a pivotal role in the development of atherosclerosis. A common polymorphism in the promoter of the IL-6 gene (IL-6 -174G>C) affects plasma IL-6 concentrations and has been suggested as a risk factor for cardiovascular disease. The aim of the present case-control study was to investigate the role of this polymorphism for retinal artery occlusion (RAO). METHODS One hundred eighty-two patients with RAO and 307 control subjects were genotyped for the IL-6 -174G>C polymorphism. Genotypes were determined by fluorogenic exonuclease (TaqMan) assay. RESULTS The prevalence of the CC genotype was significantly lower in patients with RAO than in control subjects (10.4% versus 19.9%; P=0.006). Homozygosity for the C allele was associated with an odds ratio of 0.50 (95% CI, 0.28 to 0.89) for RAO. CONCLUSIONS The CC genotype of the IL-6 -174G>C polymorphism may be associated with a protective effect against RAO.
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Affiliation(s)
- Martin Weger
- Department of Ophthalmology, Medical University, Graz, Austria
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Rankinen T, Pérusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes: the 2003 update. Med Sci Sports Exerc 2004; 36:1451-69. [PMID: 15354024 DOI: 10.1249/01.mss.0000139902.42385.5f] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
This review presents the 2003 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2003 and includes association studies with candidate genes, genome-wide scans with polymorphic markers, and single-gene defects causing exercise intolerance to variable degrees. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed but a gene or locus must be supported by at least one positive study before being inserted on the map. By the end of 2000, 29 loci were depicted on the first edition of the map. In contrast, the 2003 human gene map for physical performance and health-related phenotypes includes 109 autosomal gene entries and QTL, plus two on the X chromosome. Moreover, there are 15 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes.
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Affiliation(s)
- Tuomo Rankinen
- Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808-4124, USA.
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Effect of the G-308A polymorphism of the tumor necrosis factor (TNF)-alpha gene promoter site on plasma levels of TNF-alpha and C-reactive protein in smokers: a cross-sectional study. BMC Cardiovasc Disord 2004; 4:17. [PMID: 15485576 PMCID: PMC526204 DOI: 10.1186/1471-2261-4-17] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2004] [Accepted: 10/14/2004] [Indexed: 11/16/2022] Open
Abstract
Background Plasma levels of tumor necrosis factor (TNF)-α and of C-reactive protein (CRP) are elevated in smokers. Previous studies failed to show an association between the G-308A polymorphism in the promoter region of the TNF-α gene and coronary artery disease (CAD). We investigated whether smoking would interact with the TNF-α G-308A polymorphism in determining plasma levels of TNF-α and CRP. Methods Study participants with a complete data set in terms of smoking and the TNF-α G-308A polymorphism were 300 middle-aged male and female industrial employees. After excluding 24 irregular smokers, analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects currently smoking >3 cigarettes/day). All subjects had a fasting morning blood draw to measure plasma levels of TNF-α and CRP by high-sensitive enzyme-linked immunosorbent assays. Results The cardiovascular risk factor adjusted analysis regressing log-transformed CRP levels against smoking status, genotype, and smoking-status-genotype interaction revealed a significant main effect for smoking status (F1,250 = 5.67, p = .018) but not for genotype (F1,250 = 0.33, p = .57). The interaction-term between genotype and smoking status was not significant (F1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF-α failed to show significant main effects for smoking and genotype, as well as for the smoking-status-genotype interaction. Conclusions The findings suggest that the TNF-α G-308A polymorphism does not mediate the effect of smoking on plasma CRP levels. It remains to be seen whether other genetic polymorphisms along the inflammatory pathway may modulate vascular risk in smokers.
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Abstract
PURPOSE OF REVIEW Leukocyte invasion in the arterial wall is critical in the development of atherosclerotic lesions. This review describes recent advances in the understanding of leukocyte recruitment in atherogenesis and in the development of vulnerable plaque. It also discusses limitations in the current knowledge of this process and how these limitations may be addressed. RECENT FINDINGS The adhesive function of platelets has recently been highlighted as an important recruitment mechanism in atherosclerosis. For example, targeted deficiency of P-selectin in platelets reduces atherosclerosis in mice. Platelets also increase monocyte recruitment in atherosclerosis by secreting chemokines such as platelet factor 4 (CXCL4) or RANTES (CCL5), which trigger monocyte arrest in atherosclerotic arteries. A causal role for RANTES in atherosclerosis was shown by a protective effect of the blockage of RANTES receptors in apolipoprotein E-deficient mice. A similar effect was also demonstrated for the fractalkine receptor CX3CR1. Moreover, the classic chemoattractant LTB4 plays important roles in atherosclerosis, inasmuch as the absence of the principal LTB4 receptor (BLT1) reduces early atherosclerosis in mice. Novel data have also shown that many types of cells in lesions express 5-lipoxygenase, which indicates a rich source of leukotrienes in plaque. SUMMARY Recent data provide evidence for the involvement of several adhesive and signalling mechanisms in leukocyte recruitment in atherosclerosis. However, the specific mechanisms that are responsible for the accumulation of proatherogenic leukocytes in lesions are unclear. Detailed study of certain subclasses of leukocytes in the recruitment process will be important in future studies in this field.
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Affiliation(s)
- Einar E Eriksson
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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