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ACACβ gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes

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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 interaction between acetyl-coenzymeA carboxylase beta (ACACβ) 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 ACACβ (rs2268388) and AGTR1 (rs5186) gene polymorphism 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 ACACβ (rs2268388) and AGTR1 (rs5186) polymorphism 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 ACACβ and C allele and CC genotypes of AGTR1 were found in patients with DN as compared to patients without nephropathy. Further, T allele of ACACβ 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 genotypes of ACACβ 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.

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Acknowledgments

The part of this study was funded by Research Society for the Study of Diabetes in India (RSSDI, Grant No. 1228 to VNS). Authors are thankful to study participants and acknowledge the help rendered by Dr. Sanjay Bhadada, Dr. Pinaki Dutta, Dr. Rama Walia, Dr. Sonika, Dr. Anupam, Mr. Ravinder, and Mr. Sunil.

Conflict of interest

No competing interest to declare.

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Authors and Affiliations

  1. Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Viral N. Shah & Anil Bhansali

  2. Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Balneek Singh Cheema, Rajni Sharma & Madhu Khullar

  3. Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Harbir Singh Kohli

  4. Department of Clinical Sciences—Diabetes and Endocrinology, Lund University, Lund, Sweden

    Tarunveer Singh Ahluwalia

  5. Madras Diabetes Research Foundation, Gopalapuram, Chennai, India

    Viswanathan Mohan

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  1. Viral N. Shah
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  2. Balneek Singh Cheema
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  3. Rajni Sharma
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  4. Madhu Khullar
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  6. Tarunveer Singh Ahluwalia
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  8. Anil Bhansali
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Correspondence to Anil Bhansali.

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Shah, V.N., Cheema, B.S., Sharma, R. et al. ACACβ gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes. Mol Cell Biochem 372, 191–198 (2013). https://doi.org/10.1007/s11010-012-1460-2

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  • DOI: https://doi.org/10.1007/s11010-012-1460-2

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