Low frequency haplotypes of E-selectin polymorphisms G2692A and C1901T give increased protection from coronary artery disease
Jaroslaw Goracy, Iwona Goracy, Mariusz Kaczmarczyk, Milosz Parczewski, Miroslaw Brykczynski, Jeremy Clark, Krzysztof Safranow, Andrzej Ciechanowicz
Med Sci Monit 2011; 17(6): CR334-340
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.
Keywords: Logistic Models, Haplotypes - genetics, Environment, E-Selectin - genetics, Coronary Artery Disease - prevention & control, Case-Control Studies, Adult, Multivariate Analysis, Polymorphism, Single Nucleotide - genetics, Risk Factors