Interactive role of endothelial nitric oxide synthase gene polymorphisms in T2D with CAD and CAD patients of Punjab (North-West India)

Abstract

Dysregulation of endothelial nitric oxide synthase (eNOS) activity causes the reduction in the production of nitric oxide (NO) which is an early indicator of type 2 diabetes (T2D) and cardiovascular complications. The present study evaluates the association of −786 T > C, 894 G > T, and 4a/b polymorphisms of eNOS gene in total of 1223 individuals enrolling 307 coronary artery disease (CAD) cases, 486 T2D cases with (n = 170) and without (n = 316) CAD as the secondary macrovascular complication, and 430 healthy controls from Punjab (North-West India). Genotyping of −786 T > C and 894 G > T polymorphisms was done with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the genotyping of 4a/b insertion/deletion polymorphism was done by PCR. The minor allele frequency (MAF) of −786 T > C polymorphism was higher in CAD (21.8 %), T2D + CAD (22.4 %), and T2D cases (18.4 %) as compared to healthy controls (17.6 %). However, in single-locus analysis, no significant results were obtained for eNOS polymorphisms in any of the studied groups. Significant association of C-b-G haplotype with the risk of both CAD [P = 0.003, odds ratio (OR) = 1.89 (1.04–3.45)] and T2D [P = 0.019, OR = 1.69 (0.92–3.13)] was observed. Diplotype analysis showed that TbG/CbG haplotype combination conferred risk towards CAD and T2D [P = 0.01, OR = 2.04 (1.18–3.57); P = 0.006, OR = 2.13 (1.22–3.57), respectively]. Furthermore, phenotypic parameters like waist circumference, high-density lipoprotein, and waist to height ratio are significantly associated with 894 G > T genotypes among CAD patients. In conclusion, the eNOS polymorphisms did not provide any conclusive result individually; however, their interactive effect gives some insights towards eNOS role in the population of Punjab.