Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population

Abstract

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease, characterized by progressive albuminuria and conferring additional risk of cardiovascular disease (CVD) and mortality. The crucial role of heat-shock proteins (HSPs) on renal function in patients with DN has been well documented. The present study was aimed to understand the association of HSP-70 gene variants on the susceptibility of Type 2 Diabetes Mellitus (T2DM) and DN. A total of 946 subjects (549 Males; 397 Females) were recruited and divided into four groups according to the levels of urinary albumin excretion (UAE): those with normoalbuminuria (UAE <30 mg/24 h; n=230), those with microalbuminuria (30≤ UAE ≤300 mg/24 h; n=230), and those with macroalbuminuria (UAE> 300 mg/24 h; n=230). The control group randomly enrolled a consecutive population of 256 healthy subjects who had a routine medical check-up in our hospital. Those subjects had no history or clinical symptoms of diabetes. Subjects were genotyped for HSP70-2 (+1538 A/G; rs2763979) and HSP70-hom (+2437 C/T; rs2227956) by PCR-restriction fragment length polymorphism (RFLP). The ‘G’ allele of HSP70-2 (+1538 A/G) single nucleotide polymorphism (SNP) showed relative risk for normoalbuminuria, microalbuminuria and macroalbuminuria subjects whereas the ‘T’ allele of HSP70-hom (+2437 C/T) SNP showed significant protection against macroalbuminuria subjects. In conclusion, our results indicate that the HSP70-2 (+1538 A/G) and HSP70-hom (+2437 C/T) SNPs are highly associated with renal complications in T2DM among the South Indian population.