ACACb gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes Viral N. Shah • Balneek Singh Cheema • Rajni Sharma • Madhu Khullar • Harbir Singh Kohli • Tarunveer Singh Ahluwalia • Viswanathan Mohan • Anil Bhansali Received: 2 May 2012 / Accepted: 14 September 2012 / Published online: 19 October 2012 Ó Springer Science+Business Media New York 2012 Abstract Patients with type 2 diabetes (T2DM) are usually obese and concurrent obesity results into activation of the renin–angiotensin-system (RAS) which is a risk factor for diabetic nephropathy (DN). Gene–gene interac- tion between acetyl-coenzymeA carboxylase beta (ACACb) gene, which is involved in fatty acid metabolism and angiotensin II receptors (AGTR1) gene, which mediates RAS proteins actions on renal tissue, polymorphism with DN have not been studied earlier. The present study was designed with the aim to examine the association of an ACACb (rs2268388) and AGTR1 (rs5186) gene polymor- phism with the risk of DN in Asian Indians. 1,158 patients with T2DM belonging to two independently ascertained North Indian and one South Indian cohorts were genotyped for ACACb (rs2268388) and AGTR1 (rs5186) polymor- phism using real time PCR-based Taq-man assay and PCR–RFLP assays. In all the three cohorts, a significantly higher frequency of T allele and TT genotypes of ACACb and C allele and CC genotypes of AGTR1 were found in patients with DN as compared to patients without nephropathy. Further, T allele of ACACb and C allele of AGTR1 were found to be significantly associated with proteinuria, a hallmark of DN. We also found significant epistatic interactions between these two genes. TT geno- types of ACACb gene and CC genotype of AGTR1 gene confers the risk of DN and both genes had significant epistatic interaction in Asian Indian patients with T2DM. Keywords Acetyl-CoA carboxylase b Á Angiotensin II type 1 receptor Á Gene polymorphism Á Diabetic nephropathy Á Asian Indian Introduction Diabetes mellitus is a leading cause of end stage renal disease in developed as well as developing countries [1]. Diabetic nephropathy (DN) develops only in 35–40 % of diabetic patients and familial clustering of nephropathy in both type 1 and type 2 diabetes mellitus (T2DM) underlies the importance of genetic factors in the development and progression of DN [2]. The renin–angiotensin system (RAS) has been strongly implicated in the pathogenesis of progressive renal diseases [3]. RAS plays a central role in the regulation of blood pressure, sodium homeostasis, and renal hemodynamics. Its action is mediated primarily by angiotensin II which acts on type 1 angiotensin II receptors (AGTR1) in the vasculature, leading to vasoconstriction, and on the zona glomerulosa, where it stimulates the secretion of aldoste- rone and leading to mesengial fibrosis [4]. Adipocytes do V. N. Shah Á A. Bhansali (&) Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India e-mail: anilbhansali_endocrine@rediffmail.com B. S. Cheema Á R. Sharma Á M. Khullar Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India H. S. Kohli Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India T. S. Ahluwalia Department of Clinical Sciences—Diabetes and Endocrinology, Lund University, Lund, Sweden V. Mohan Madras Diabetes Research Foundation, Gopalapuram, Chennai, India 123 Mol Cell Biochem (2013) 372:191–198 DOI 10.1007/s11010-012-1460-2