Genetic susceptibility to coronary artery disease in type 2 diabetic patients. (c2010)

Abstract

Type 2 diabetes is a major risk factor for coronary artery disease (CAD). Diabetic patients are three times more likely to develop CAD than non-diabetic individuals. Many genes have been studied to test for an association between the different gene variants with CAD in individuals with type 2 diabetes. Of these genes, we selected the most relevant ones including a common allele on chromosome 9p21 (rs2383206), a variant in the uncoupling protein 2 (UCP2) promoter (rs659366), a genetic marker in the potassium voltage gated channel KCNQ1 gene (rs2237892), a proteasome subunit alpha type 6 (PSMA6) gene variant in 5' untranslated region of exon 1 (rs1048990), and the polymorphism in 5' untranslated region of the vascular endothelial growth factor (VEGF) gene (rs2010963). Our purpose is to validate in a Lebanese population the association between these five single nucleotide polymorphisms (SNPs) and CAD in subjects with type 2 diabetes. We selected 752 subjects (352 patients with type 2 diabetes of whom 199 had CAD and 400 subjects without type 2 diabetes of whom 202 had CAD) were genotyped for variants of the 9p21 locus, UCP2 gene, KCNQl gene, PSMA6 gene, and VEGF gene. Genotype and allele frequencies between the patients and the control groups were compared using chi-square and logistic regression analyses. In the type 2 diabetic population, allele frequency and Genotype distribution did not differ between CAD patients and controls of the SNPs at the 9p21 region, UCP2 promoter, KCNQ1 gene, PSMA6 gene, or VEGF gene. When we restricted the analysis to non-diabetic patients (n =400), significant results were obtained in the PSMA6-rsl048990 and the VEGFrs2010963 polymorphism when comparing subjects with CAD to controls without CAD (p = 0.027, P = 0.036 respectively). An inverse association between CAD and the GG+GC genotype (OR=0.61) as well as the G allele (OR=0.66) of the PSMA6 polymorphism were observed in the non-diabetic population. In addition, the CC genotype of the VEGF-rs2010963 polymorphism associated with CAD in a recessive model in the non-diabetic population (OR=1.89). In Conclusion, we could not replicate in a Lebanese population, the associations of the five SNPs studied with CAD in a diabetic population. However, our study suggests that the GG+GC genotypes and the G allele of PSMA6-rsl048990 might be protective against CAD and that the CC genotype ofVEGF-rs2010963 could be possible a marker of CAD in a non-diabetic Lebanese population.