Polymorphisms in Mn-SOD and EC-SOD gene and risk of nephropathy in Western Indian Type 2 diabetic patients

Abstract

Single-nucleotide polymorphisms in genes related to oxidative stress are a risk factor for the development of diabetes and its complications. The allele and genotype frequencies of missense polymorphism Ala-9Val and Val16Ala in Mn-SOD and Arg213Gly in EC-SOD genes were studied in (a) patients with Type 2 diabetes mellitus (T2DM) without any complication (T2DM), (b) diabetic nephropathy (DN), (c) non-diabetic nephropathy (NDN) and (d) control healthy subjects from Western region of India. The PCR products were digested with BshTI, BsaWI and Eco52I restriction enzymes to detect Ala-9Val, Val16Ala and Arg213Gly polymorphisms respectively. The frequency of Val allele of Ala-9Val (P = 0.568 and P = 0.571) and Ala allele of Val16Ala (P = 0.993 and P = 0.152) polymorphisms of Mn-SOD gene did not show a significant difference in patient with T2DM and NDN compared to control subjects respectively. Frequency of Val allele of Ala-9Val (42.8 % vs. 61.5 %, P < 0.001) and Ala allele of Val16Ala (39.0 % vs. 53.5 %, P = 0.005) polymorphisms of Mn-SOD gene was significantly higher in patients with DN than that of patient with T2DM. For Arg213Gly polymorphism of EC-SOD gene, the Gly allele frequency in T2DM and NDN group did not significantly (P = 0.993 and P = 0.152 respectively) differ from control subjects as well as non-significantly higher in DN compared to T2DM. These results suggests that Ala-9Val and Val16Ala polymorphism in Mn-SOD is not involved in development of diabetes but may play a crucial role in determining genetic susceptibility to diabetic nephropathy in Western Indian Type 2 diabetic patients. Our data found a lack of association of EC-SOD (Arg213Gly) polymorphism with development of diabetes and diabetic nephropathy.