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Steiner CA, Berinstein JA, Louissaint J, Higgins PDR, Spence JR, Shannon C, Lu C, Stidham RW, Fletcher JG, Bruining DH, Feagan BG, Jairath V, Baker ME, Bettenworth D, Rieder F. Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review. Clin Gastroenterol Hepatol 2022; 20:817-846.e10. [PMID: 34089850 PMCID: PMC8636551 DOI: 10.1016/j.cgh.2021.05.054] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/20/2021] [Accepted: 05/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. METHODS We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). RESULTS Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. CONCLUSIONS There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
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Affiliation(s)
- Calen A Steiner
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
| | - Jeffrey A Berinstein
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Jeremy Louissaint
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Peter D R Higgins
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Jason R Spence
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan
| | - Carol Shannon
- Taubman Health Sciences Library, University of Michigan, Ann Arbor, Michigan
| | - Cathy Lu
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Ryan W Stidham
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan
| | | | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Brian G Feagan
- Alimentiv Inc, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Biostatistics and Epidemiology, Western University, London, Ontario, Canada
| | - Vipul Jairath
- Alimentiv Inc, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Biostatistics and Epidemiology, Western University, London, Ontario, Canada
| | - Mark E Baker
- Section of Abdominal Imaging, Imaging Institute, Digestive Diseases and Surgery Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University of Münster, Münster, Germany
| | - Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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Balbino KP, Hermsdorff HHM, Bressan J. Polymorphism related to cardiovascular risk in hemodialysis subjects: a systematic review. J Bras Nefrol 2018; 40:179-192. [PMID: 29944163 PMCID: PMC6533983 DOI: 10.1590/2175-8239-jbn-3857] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/23/2017] [Indexed: 02/01/2023] Open
Abstract
Cardiovascular disease (CVD) is one of the leading causes of mortality in hemodialysis (HD) subjects. In addition to the traditional risk factors that are common in these individuals, genetic factors are also involved, with emphasis on single nucleotide polymorphs (SNPs). In this context, the present study aims to systematically review the studies that investigated the polymorphisms associated with cardiovascular risk in this population. In general, the SNPs present in HD individuals are those of genes related to inflammation, oxidative stress and vascular calcification, also able of interfering in the cardiovascular risk of this population. In addition, polymorphisms in genes related to recognized risk factors for CVD, such as dyslipidemia, arterial hypertension and left ventricular hypertrophy, also influence cardiovascular morbidity and mortality.
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Affiliation(s)
- Karla Pereira Balbino
- Universidade Federal de Viçosa, Departamento de Nutrição e Saúde,
Viçosa, MG, Brasil
| | | | - Josefina Bressan
- Universidade Federal de Viçosa, Departamento de Nutrição e Saúde,
Viçosa, MG, Brasil
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Srivastava K, Chandra S, Narang R, Bhatia J, Saluja D. E-selectin gene in essential hypertension: a case-control study. Eur J Clin Invest 2018; 48. [PMID: 29178542 DOI: 10.1111/eci.12868] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 11/21/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND Hypertension is associated with endothelial cell dysfunction. E-selectin, an endothelial cell adhesion molecule, is specific for endothelial cell activation. Polymorphism in E-selectin gene has recently been identified among which Leu554Phe E-selectin gene polymorphism is least investigated in essential hypertension. This study reports the association of E-selectin gene Leu554Phe polymorphism and the expression of E-selectin gene in patients with essential hypertension. MATERIALS AND METHODS We analysed the Leu554Phe polymorphism and expression of E-selectin gene in 250 patients with essential hypertension and 250 normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of E-selectin gene at mRNA and protein levels were carried out by real-time PCR and Western blot, respectively. RESULTS A significant association of E-selectin genotypes (CT + TT) with essential hypertension (P < .0001, Odds ratio = 2.2 [1.58-3.24] at 95% CI) was observed. The expression of mRNA for E-selectin gene in patients with essential hypertension was ~12-fold higher as compared to control. We observed an elevated level of E-selectin protein expression (up to 1.9 times) in patients as compared to controls. CONCLUSIONS A significant association of E-selectin (Leu554Phe) gene and increased expression of E-selectin gene at mRNA and protein levels in patients might be related to the genetic predisposition to develop essential hypertension.
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Affiliation(s)
- Kamna Srivastava
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
| | - Sudhir Chandra
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
| | - Rajiv Narang
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Jagriti Bhatia
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
| | - Daman Saluja
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
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Horodyska J, Hamill RM, Varley PF, Reyer H, Wimmers K. Genome-wide association analysis and functional annotation of positional candidate genes for feed conversion efficiency and growth rate in pigs. PLoS One 2017; 12:e0173482. [PMID: 28604785 PMCID: PMC5467825 DOI: 10.1371/journal.pone.0173482] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 05/24/2017] [Indexed: 01/03/2023] Open
Abstract
Feed conversion efficiency is a measure of how well an animal converts feed into live weight and it is typically expressed as feed conversion ratio (FCR). FCR and related traits like growth rate (e.g. days to 110 kg—D110) are of high interest for animal breeders, farmers and society due to implications on animal performance, feeding costs and environmental sustainability. The objective of this study was to identify genomic regions associated with FCR and D110 in pigs. A total of 952 terminal line boars, showing an individual variation in FCR, were genotyped using 60K SNP-Chips. Markers were tested for associations with estimated breeding values (EBV) for FCR and D110. For FCR, the largest number of associated SNPs was located on chromosomes 4 (30 SNPs), 1 (25 SNPs), X (15 SNPs) and 6 (12 SNPs). The most prominent genomic regions for D110 were identified on chromosomes 15 (10 SNPs), 1 and 4 (both 9 SNPs). The most significantly associated SNPs for FCR and D110 mapped 129.8 Kb from METTL11B (chromosome 4) and 32Kb from MBD5 (chromosome 15), respectively. A list of positional genes, closest to significantly associated SNPs, was used to identify enriched pathways and biological functions related to the QTL for both traits. A number of candidate genes were significantly overrepresented in pathways of immune cell trafficking, lymphoid tissue structure, organ morphology, endocrine system function, lipid metabolism, and energy production. After resequencing the coding region of selected positional and functional candidate genes, six SNPs were genotyped in a subset of boars. SNPs in PRKDC, SELL, NR2E1 and AKRIC3 showed significant associations with EBVs for FCR/D110. The study revealed a number of chromosomal regions and candidate genes affecting FCR/D110 and pointed to corresponding biological pathways related to lipid metabolism, olfactory reception, and also immunological status.
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Affiliation(s)
- Justyna Horodyska
- Teagasc, Food Research Centre, Ashtown, Dublin, Ireland
- Leibniz Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Dummerstorf, Germany
| | | | | | - Henry Reyer
- Leibniz Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Dummerstorf, Germany
- * E-mail:
| | - Klaus Wimmers
- Leibniz Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Dummerstorf, Germany
- Faculty of Agricultural and Environmental Sciences, University Rostock, Rostock, Germany
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Israeli E, Goldin E, Fishman S, Konikoff F, Lavy A, Chowers Y, Melzer E, Lahat A, Mahamid M, Shirin H, Nussinson E, Segol O, Ya'acov AB, Shabbat Y, Ilan Y. Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial. Clin Exp Immunol 2015; 181:362-72. [PMID: 25846055 DOI: 10.1111/cei.12640] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Revised: 03/17/2015] [Accepted: 03/17/2015] [Indexed: 12/18/2022] Open
Abstract
Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.
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Affiliation(s)
- E Israeli
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem
| | - E Goldin
- Department of Gastroenterology, Shaarei Zedek Medical Center, Jerusalem
| | - S Fishman
- Department of Gastroenterology, Tel Aviv-Sourasky Medical Center, Tel Aviv
| | - F Konikoff
- Department of Gastroenterology, Meir Medical Center, Kfar Saba
| | - A Lavy
- Department of Gastroenterology, Bnai Zion Hospital, Haifa
| | - Y Chowers
- Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa
| | - E Melzer
- Department of Gastroenterology, Kaplan Medical Center, Rehovot
| | - A Lahat
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer
| | - M Mahamid
- Department of Gastroenterology, Holy Family Hospital, Nazareth
| | - H Shirin
- Department of Gastroenterology, Assaf Harofeh Medical Center, Zerifin
| | - E Nussinson
- Department of Gastroenterology, Ha'emek Medical Center, Afula
| | - O Segol
- Department of Gastroenterology, Carmel Medical Center, Haifa, Israel
| | - A Ben Ya'acov
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem
| | - Y Shabbat
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem
| | - Y Ilan
- Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem
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Song GG, Lee YH. The Polymorphisms K469E and G261R of Intercellular Adhesion Molecule-1 and Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis. Immunol Invest 2015; 44:361-72. [DOI: 10.3109/08820139.2015.1010685] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Issac MSM, Afif A, Gohar NA, Fayek NAF, Zayed B, Sedrak H, Salah El Din LA. Association of E-selectin gene polymorphism and serum PAPP-A with carotid atherosclerosis in end-stage renal disease. Mol Diagn Ther 2014; 18:243-52. [PMID: 24151105 DOI: 10.1007/s40291-013-0061-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Atherosclerotic vascular disease represents a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The endothelium plays a crucial role in vascular inflammation. E-selectin is exclusively expressed on activated endothelial cells and is upregulated following an inflammatory response and oxidative stress, while serum pregnancy-associated plasma protein-A (PAPP-A) concentrations are related to the presence and stability of carotid atherosclerotic plaques. OBJECTIVE The aim of this study was to investigate whether there is an association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and the presence of carotid atherosclerosis in ESRD patients. SUBJECTS AND METHODS Seventy subjects were recruited into this study; 40 ESRD patients [age (mean ± SD) 43.42 ± 13.94 years] and 30 age- and gender-matched healthy individuals assigned to the control group. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of SELE rs5355C>T gene polymorphism, while serum PAPP-A concentrations were measured using electro-chemiluminescence immunoassay. Routine laboratory tests were measured on an automated chemistry analyzer. Carotid ultrasonographic studies were performed by a bilateral high-resolution B-mode ultrasound. RESULTS There was no significant relationship between the SELE rs5355C>T gene polymorphism and ESRD incidence. Serum PAPP-A levels were significantly higher in ESRD patients compared with controls [median (interquartile range) 5.8 (5.1-11.6) and 5.1 (4.1-6.7), respectively; p = 0.005]. Serum PAPP-A correlated positively with urea, creatinine, systolic and diastolic blood pressure (DBP). Serum PAPP-A showed a statistically significant increase in SELE rs5355TT versus CC in both patients and controls. There was no association on comparing right intima-media thickness (IMT), left IMT, right cross-sectional area (CSA) and left CSA with the CC, CT and TT genotypes of SELE rs5355C>T. No correlation between serum PAPP-A with each of the above-mentioned carotid doppler findings was observed. There was a statistically significant increase in DBP in TT genotype carriers when compared with CC genotype carriers (p = 0.009). Serum PAPP-A levels were higher in hypertensive ESRD patients when compared with normotensive ESRD patients. There was a statistically significant decrease in high-density lipoprotein cholesterol (HDL-C) in TT genotype carriers when compared with CT genotype carriers in the whole study group (p = 0.003). Serum PAPP-A correlated negatively with HDL-C. CONCLUSION The lack of a direct association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and IMT suggests that their hypothesized association with carotid atherosclerosis might reflect an indirect mechanism of SELE rs5355C>T gene polymorphism and serum PAPP-A with cardiovascular risk factors such as blood pressure and HDL-C rather than a direct effect on the vasculature.
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Affiliation(s)
- Marianne Samir M Issac
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, El Saray St., El Manial, Cairo, 11956, Egypt,
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Ouyang Y, Wu H, Tan A, Yang H, Gao Y, Li H, Lu S, Hu Y, Tang X, Zhang H. E-selectin gene polymorphism (A561C) and essential hypertension. Meta-analysis in the Chinese population. Herz 2014; 40 Suppl 2:197-202. [PMID: 25171839 DOI: 10.1007/s00059-014-4122-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Revised: 05/21/2014] [Accepted: 05/22/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND The A561C polymorphism of the E-selectin gene (SELE) has been reported to be associated with essential hypertension (EH) in several studies; however, results among these studies were inconsistent. Here, we conducted a meta-analysis to explore the association of the A561C polymorphism with EH. METHODS Publications were retrieved through searching PubMed, Web of Science, the China National Knowledge Infrastructure (CNKI), China Biological Medicine, and the Wanfang database. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated to estimate the strength of association of A561C with EH. Subgroup analysis was also performed to assess ethnic discrepancies. A total of seven studies comprising 2,127 EH patients and 2,078 controls were analyzed. RESULTS In the dominant model analysis, we found significant associations between the A561C polymorphism and EH in all subjects (CC+AC vs. AA, OR = 1.96, 95 %CI 1.57-2.44, P heterogeneity = 0.381), in a Han Chinese subgroup (CC+AC vs. AA, OR = 2.38, 95 %CI 1.73-3.29, P heterogeneity = 0.269), and in non-Han Chinese minorities (CC+AC vs. AA, OR = 1.62, 95 %CI 1.19-2.21, P heterogeneity = 0.84). CONCLUSION The findings suggest that C allele carriers of the SELE gene polymorphism (A561C) might be predisposed to EH in the Chinese population. Further investigations in other ethnic populations should be conducted to verify these findings.
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Affiliation(s)
- Y Ouyang
- School of Public Health of Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, China
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Sarlos P, Kovesdi E, Magyari L, Banfai Z, Szabo A, Javorhazy A, Melegh B. Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature. World J Gastrointest Pathophysiol 2014; 5:304-21. [PMID: 25133031 PMCID: PMC4133528 DOI: 10.4291/wjgp.v5.i3.304] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 03/19/2014] [Accepted: 07/12/2014] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.
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Wang T, Ji X, Luo C, Fan J, Hou Z, Chen M, Han R, Ni C. Polymorphisms in SELE gene and risk of coal workers' pneumoconiosis in Chinese: a case-control study. PLoS One 2013; 8:e73254. [PMID: 24066042 PMCID: PMC3774684 DOI: 10.1371/journal.pone.0073254] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 07/18/2013] [Indexed: 12/14/2022] Open
Abstract
Background Coal workers' pneumoconiosis (CWP) is characterized by chronic pulmonary inflammation and fibrotic nodular lesions that usually lead to progressive fibrosis. Inflammation is the first step in the development of CWP. E-selectin, an adhesion molecule, is involved in the development of various inflammatory diseases. Methods We investigated the association between the functional polymorphisms in SELE and the risk of CWP in Han Chinese population. Three polymorphisms (T1880C/rs5355, T1559C/rs5368, A16089G/rs4786) in SELE were genotyped and analyzed in a case-control study with 697 CWP cases and 694 controls. The genotyping was based on the TaqMan method with the ABI 7900HT Real Time PCR system. Results The SELE rs5368 CT genotype was associated with a significantly increased risk of CWP (OR = 1.28, 95% CI = 1.02–1.60, P = 0.03) relative to the CC genotype. The statistical analysis of classification and regression tree (CART) and multifactor dimensionality reduction (MDR) were used to predict the interactions among risk factors of CWP. The MDR analysis found that the best interaction model was the two-factor model that contains pack-years smoked and SELE rs5368 genotypes. For non-smokers, the CART analysis showed an increased risk of CWP for carriers of the SELE rs_5368 variant genotype compared with the common genotype (OR = 1.51; 95% CI = 1.11–2.05, P = 0.0069). Conclusion The results suggest that the T1559C/rs5368 polymorphism and smoking are involved in the susceptibility to CWP. Further studies are warranted to validate these findings.
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Affiliation(s)
- Ting Wang
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiaoming Ji
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Chen Luo
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jingjing Fan
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Zhiguo Hou
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Minjuan Chen
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Ruhui Han
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Chunhui Ni
- Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China
- * E-mail:
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Liarmakopoulos E, Gazouli M, Aravantinos G, Theodoropoulos G, Rizos S, Vaiopoulou A, Kouraklis G, Nikiteas N. E-Selectin S128R gene polymorphism in gastric cancer. Int J Biol Markers 2013; 28:38-42. [PMID: 23015400 DOI: 10.5301/jbm.2012.9582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2012] [Indexed: 11/20/2022]
Abstract
BACKGROUND E-selectin is an adhesion molecule expressed on activated endothelial cells. E-selectin plays an important role in the process of inflammation and is also involved in the mechanism of cancer metastasis regulating the adhesion of circulating cancer cells to the blood vessels. The aim of our study was to determine whether an association exists between its most common gene polymorphism, S128R, and gastric cancer (GC).
METHODS We performed a case-control study of 88 GC cases and 480 controls to analyze the association between E-selectin S128R gene polymorphism and GC susceptibility. The genotyping analysis was done by PCR-restriction fragment length polymorphism method.
RESULTS The E-selectin S128R C allele, CA and CC genotypes were over-represented among the GC cases. No statistically significant association was observed between E-selectin S128R polymorphisms and tumor characteristics. However, carrying the C allele was associated with poor survival.
CONCLUSIONS The E-selectin S128R C allele may confer an increased susceptibility to gastric cancer development and correlate with a poor prognosis.
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Scott DW, Patel RP. Endothelial heterogeneity and adhesion molecules N-glycosylation: implications in leukocyte trafficking in inflammation. Glycobiology 2013; 23:622-33. [PMID: 23445551 DOI: 10.1093/glycob/cwt014] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Inflammation is a major contributing element to a host of diseases with the interaction between leukocytes and the endothelium being key in this process. Much is understood about the nature of the adhesion molecule proteins expressed on any given leukocyte and endothelial cell that modulates adhesive interactions. Although it is appreciated that these proteins are heavily glycosylated, relatively little is known about the roles of these posttranslational modifications and whether they are regulated, and if so how during inflammation. Herein, we suggest that a paucity in this understanding is one major reason for the lack of successful therapies to date for modulating leukocyte-endothelial interactions in human inflammatory disease and discuss developing paradigms of (i) how endothelial adhesion molecule glycosylation (with a focus on N-glycosylation) maybe a critical element in understanding endothelial heterogeneity between different vascular beds and species, (ii) how adhesion molecule N-glycosylation may be under distinct, and as yet, unknown modes of regulation during inflammatory stress to affect the inflammatory response in a vascular bed- and disease-specific manner (analogous to a "zip code" for inflammation) and finally (iii) to underscore the concept that a fuller appreciation of the role of adhesion molecule glycoforms is needed to provide foundations for disease and tissue-specific targeting of inflammation.
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Affiliation(s)
- David W Scott
- Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, 901 19th St. South, BMRII 532, Birmingham, AL 35294, USA
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Selectins and Associated Adhesion Proteins in Inflammatory disorders. ANIMAL LECTINS: FORM, FUNCTION AND CLINICAL APPLICATIONS 2012. [PMCID: PMC7121831 DOI: 10.1007/978-3-7091-1065-2_44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Inflammation is defined as the normal response of living tissue to injury or infection. It is important to emphasize two components of this definition. First, that inflammation is a normal response and, as such, is expected to occur when tissue is damaged. Infact, if injured tissue does not exhibit signs of inflammation this would be considered abnormal and wounds and infections would never heal without inflammation. Secondly, inflammation occurs in living tissue, hence there is need for an adequate blood supply to the tissues in order to exhibit an inflammatory response. The inflammatory response may be triggered by mechanical injury, chemical toxins, and invasion by microorganisms, and hypersensitivity reactions. Three major events occur during the inflammatory response: the blood supply to the affected area is increased substantially, capillary permeability is increased, and leucocytes migrate from the capillary vessels into the surrounding interstitial spaces to the site of inflammation or injury. The inflammatory response represents a complex biological and biochemical process involving cells of the immune system and a plethora of biological mediators. Cell-to-cell communication molecules such as cytokines play an extremely important role in mediating the process of inflammation. Inflammation and platelet activation are critical phenomena in the setting of acute coronary syndromes. An extensive exposition of this complex phenomenon is beyond the scope of this article (Rankin 2004).
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Wang Z, Liu Y, Liu J, Liu K, Lou Y, Wen J, Niu Q, Wen S, Wu Z. E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population. BMC MEDICAL GENETICS 2010; 11:127. [PMID: 20796317 PMCID: PMC2940768 DOI: 10.1186/1471-2350-11-127] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2010] [Accepted: 08/27/2010] [Indexed: 11/23/2022]
Abstract
Background Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension. Methods Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study. Results Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C). Conclusion C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.
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Affiliation(s)
- Zuoguang Wang
- Department of Hypertension, Beijing Anzhen Hospital, Attached to Capital University of Medical Sciences, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing, 100029, China
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Vainer B. Intercellular adhesion molecule-1 (ICAM-1) in ulcerative colitis: presence, visualization, and significance. APMIS 2010:1-43. [PMID: 20653648 DOI: 10.1111/j.1600-0463.2010.02647.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Ben Vainer
- Department of Pathology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
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Abstract
PURPOSE OF REVIEW One of the significant limitations to the investigation of inflammatory bowel disease (IBD) in humans is the impossibility of studying this condition from the beginning of the disease process to understand the individual contribution of the various microbiological and immunological components to its pathogenesis. Pouchitis can serve as a human model for IBD, as the time of the pouch creation is known, which allows to prospectively study the events that might eventually lead to the development of a form of intestinal inflammation (i.e., pouchitis) that mimics IBD. RECENT FINDINGS A considerable amount of progress has been made in the last few years on the mechanisms underlying the pathogenesis of pouchitis. Recent literature suggests that pouchitis may present a spectrum of disease processes, with a wide range of causes, risk factors, clinical phenotypes, disease courses, and prognoses. Genetic, microbiological, and immunological profiles in pouchitis were evaluated. SUMMARY Ileal pouch and pouchitis represent a valuable human model to study the evolution of bacterial communities and host-bacteria interactions in IBD by sequentially monitoring microbiological and immunological profile before, during, and after pouch construction and before and after development and treatment of pouchitis.
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