Genetic association of NAD(P)H quinone oxidoreductase (NQO1*2) polymorphism with NQO1 levels and risk of diabetic nephropathy

Abstract

Abstract NAD(P)H quinone oxidoreductase 1 (NQO1) catalyzes reactions having a cyto-protective effect against redox cycling and oxidative stress. A single base polymorphism (C/T) at nucleotide 609 of the NQO1 gene impairs the stability and function of its protein. Its role in the development of diabetic nephropathy (DN) has not been deciphered. Therefore, this study aimed to evaluate the association of NQO1*2 (rs1800566) polymorphism with plasma NQO1 levels and DN. This study screened 600 participants including healthy controls (HC), type 2 diabetes mellitus without complications (T2DM) and diabetic nephropathy (DN): 200 each for studying NQO1*2 gene polymorphism using the PCR-RFLP. Plasma NQO1 levels were measured by ELISA. Analysis of variance and logistic regression were used to evaluate the association of NQO1 polymorphism with plasma NQO1 levels and DN. The allelic frequencies of NQO1*1/NQO1*2 were 0.88/0.12 in HC, 0.765/0.235 in T2DM and 0.65/0.35 in DN. Carriers of the NQO1*2 allele had significantly lower plasma NQO1 levels (p<0.05) and revealed higher risk towards the development of DN (OR=1.717, p=0.010). NQO1*2 SNP is a functional polymorphism having a significant effect on NQO1 levels. Our results indicate that NQO1*2 genotype may increase susceptibility to DN in north Indian subjects with T2DM.