CYP2D6 (C2850T, G1846A, C100T) polymorphisms, haplotypes and MDR analysis in predicting coronary artery disease risk in north-west Indian population: A case-control study.

AIMS: 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.

METHODS: 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.

RESULTS: 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.

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