Dataset Information

Low frequency haplotypes of E-selectin polymorphisms G2692A and C1901T give increased protection from coronary artery disease.

ABSTRACT: BACKGROUND: E-selectin polymorphisms are an independent atherosclerosis and coronary artery disease (CAD) risk factor. This study aimed to investigate the link between the C1901T and G2692A E-selectin tagging SNPs and their haplotypes and the extent of coronary artery disease in Polish patients. MATERIAL/METHODS: For this study 321 patients were recruited CAD extent by coronary angiography and E selectin gene variant were investigated using HapMap, PCR/RFLP, multivariate logistic regression and haplotype analysis. RESULTS: Frequency distributions of the C1901T and G2692A polymorphisms were significantly different in CAD patients as compared to control subjects (p=0.037 and p=0.025, respectively). The C1901T polymorphism was found to be an independent genetic predictor of risk of CAD (OR=3.01) in a multivariate model adjusted for classic, environmental risk factors. The A-C and G-T haplotypes showed the strongest significant associations with CAD. The A-C haplotype proved to be significantly more common in controls (haplotype frequency 9.2%) than in CAD (5.7%, p=0.048); the G-T haplotype was not found among control subjects (0.0%) but was found in CAD (1.3%, p=0.0099). CONCLUSIONS: Associations between the C1901T and G2692A E-selectin polymorphisms and CAD in the Polish population were found. Investigated variants correlated with the risk of coronary artery disease development but not with the extent of coronary artery vascular changes. In the haplotype analysis, 2 haplotypes influenced CAD--the A-C haplotype (7%) proved to exert a protective effect against CAD, while the effect of the less frequent G-T haplotype (1%) was associated with significant increase in CAD risk.

SUBMITTER: Goracy J

PROVIDER: S-EPMC3539538 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Low frequency haplotypes of E-selectin polymorphisms G2692A and C1901T give increased protection from coronary artery disease.

Gorący Jarosław J Gorący Iwona I Kaczmarczyk Mariusz M Parczewski Miłosz M Brykczyński Mirosław M Clark Jeremy J Safranow Krzysztof K Ciechanowicz Andrzej A

Medical science monitor : international medical journal of experimental and clinical research 20110601 6

<h4>Background</h4>E-selectin polymorphisms are an independent atherosclerosis and coronary artery disease (CAD) risk factor. This study aimed to investigate the link between the C1901T and G2692A E-selectin tagging SNPs and their haplotypes and the extent of coronary artery disease in Polish patients.<h4>Material/methods</h4>For this study 321 patients were recruited CAD extent by coronary angiography and E selectin gene variant were investigated using HapMap, PCR/RFLP, multivariate logistic re ...[more]

PMID: 21629188

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Project description:BackgroundThe selectins play important roles in the inflammatory process of coronary artery disease (CAD) and myocardial infarction (MI). Previous studies have shown ambiguous findings regarding a possible association between the selectin genes and CAD. The E-selectin Ser128Arg polymorphism and the P-selectin Thr715Pro polymorphism have been investigated widely but with inconsistent results. We performed a comprehensive meta-analysis to shed light on this issue.MethodsData were extracted by searches of MEDLINE, Embase, CNKI, Wanfang, Google Scholar, PORTA, GeNii, CiNii, J-STAGE, Nurimedia and Koreanstudies Information Service System [Kiss] up to October 2013, in which 10 studies on the Ser128Arg polymorphism with 3369 cases and 2577 controls and 10 studies on the Thr715Pro polymorphism with 5886 cases and 18345 controls. A random-effects model was used to calculate the combined odds ratios. The between-study heterogeneity and publication bias were addressed.ResultsThe 128Arg carriers had a significant increased risk of CAD (allele comparison: P?=?0.02, OR?=?1.33, 95%CI 1.04-1.69, P(heterogeneity)?=?0.01); The 715Pro conferred a non-significant risk reduction relative to the 715Thr (allele comparison: P?=?0.40, OR?=?0.94, 95%CI 0.82-1.08, P(heterogeneity)?=?0.03).Subgroup analyses demonstrated that the 128Arg carriers had a significant increased risk of CAD among Asians (allele comparison: P?=?0.001, OR?=?2.07, 95%CI 1.33-3.24, P(heterogeneity)?=?0.77) but not among Caucasians (allele comparison: P?=?0.33, OR?=?1.13, 95%CI 0.88-1.45, P(heterogeneity)?=?0.08). Carrier status for the 715Pro was significantly associated with reduced risk of MI (allele comparison: P?=?0.04, OR?=? 0.81, 95%CI 0.67-0.99, P(heterogeneity?)=?0.14). The asymmetric funnel plot and the Egger's test (P?=?0.041) suggested the presence of publication bias for the Ser128Arg polymorphism.ConclusionOur results suggested there is an increase in the risk of CAD conferred by the Ser128Arg polymorphism and the thr715Pro polymorphism may be a protective factor of MI.

Project description:ObjectiveE-selectin (SELE) mediates the rolling and adhesion of leukocytes on activated endothelial cells and plays a critial role in the pathogenesis of coronary artery disease (CAD). Associatons between the A561C and G98T polymorphisms of the SELE gene and CAD risk were investigated broadly, but the results were inconsistent. In the present study, we performed a meta-analysis to systematically evaluate the associations between the two polymorphisms and the risk of CAD.MethodsComprehensive research was conducted to identify relevant studies. The fixed or random effect model was selected based on the heterogeneity among studies, which was evaluated with Q-test and ?(2). Meta-regression was used to explore the potential sources of between-study heterogeneity. Peters's linear regression test was used to estimate the publication bias.ResultsOverall, 24 articles involving 3694 cases and 3469 controls were included. After excluding articles deviating from Hardy-Weinberg equilibrium in controls and sensitive analysis, our meta-analysis showed a significant association between the A561C ploymprphism and CAD in dominant (OR=?1.84, 95% CI?=?1.56-2.16) and codominant (OR=?1.74, 95% CI=?1.49-2.03) models. As for the G98T polymorphism, significantly increased CAD risk was observed in dominant (OR?=?1.47, 95% CI=?1.16-1.87) and codominant (OR=?1.48, 95% CI?=?1.18-1.86) models, but after subgroup analysis, the association was not significant among Caucasians in dominant (OR=?1.58, 95% CI=?0.73-3.41) and codominant (OR=?1.58, 95% CI=?0.79-3.20) models.ConclusionsDespite some limitations, our meta-analysis suggested that the SELE gene polymorphisms (A561C, G98T) were significantly associated with increased risk of CAD. However, after subgroup analysis no significant association was found among Caucasians for the G98T polymorphism, which may be due to the small sample size and other confounding factors. Future investigations with multicenter, large-scale, and multi-ethnic groups are needed.

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Dataset Information

Low frequency haplotypes of E-selectin polymorphisms G2692A and C1901T give increased protection from coronary artery disease.

Publications

Low frequency haplotypes of E-selectin polymorphisms G2692A and C1901T give increased protection from coronary artery disease.

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