CYP2D6 (C2850T, G1846A, C100T) polymorphisms, haplotypes and MDR analysis in predicting coronary artery disease risk...

The present study was aimed to evaluate the association of C2850T, G1846A and C100T polymorphisms of the CYP2D6 with coronary artery disease (CAD) in North-West Indian population.

In this case-control study, 200 patients with CAD and 200 age-, gender- and ethnicity-matched healthy controls were genotyped for C2850T, G1846A and C100T polymorphisms of CYP2D6 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Genotype and allele distributions of C2850T and G1846A polymorphisms of the CYP2D6 were significantly different between cases and controls (p = 0.038, p = 0.021; p = 0.048, p = 0.012, respectively) whereas the distribution of genotype and allele for C100T polymorphism did not differ significantly (p = 0.098, p = 0.117, respectively). The 2850T and1846A variants were significantly associated with the increased risk of developing CAD, as observed from the odds ratios for the 2850 T/T and 1846 G/A genotypes (OR: 2.44, 95% CI: 1.99-4.99, p = 0.015 and OR: 1.62, 95% CI: 1.02-2.56, p = 0.041, respectively). Moreover, the recessive model in C2850T and the dominant model in G1846A are the best fit inheritance models to predict the susceptible gene effects (OR: 2. 07, 95% CI: 1.05-4.08, p = 0.031 and OR: 1.70, 95% CI: 1.10-2.62, p = 0.016, respectively). On gender stratification, these associations were observed only in females in addition to the C/T genotype of C2850T (OR: 2.52, 95% CI: 1.42-4.38, p = 0.001) and C100T (OR: 3.18, 95% CI: 1.52-6.67, p = 0.002). Furthermore, it is also observed that the CAT (OR: 2. 61, 95% CI: 1.07-6.34, p = 0.035) and TAC (OR: 15. 22, 95% CI: 1.97-117.58, p = 0.009) are high-risk haplotypes for CAD in the total group, whereas, the TGC (OR: 1. 64, 95% CI: 1.02-2.62, p = 0.042) and CAT (OR: 4. 21, 95% CI: 1.12-15.59, p = 0.035) haplotypes provide gender-specific risk in females.

Our results indicate significant association of C2850T, G1846A and C100T polymorphisms of CYP2D6 with CAD especially in females of North-West Indian population.