Journal of Diabetes and Its Complications
Volume 23, Issue 2 , Pages 102-111, March 2009

Oxidative stress pathway genes and chronic renal insufficiency in Asian Indians with Type 2 diabetes☆

  • Arun K. Tiwari

      Affiliations

    • Department of Genetics, University of Delhi South Campus, New Delhi 110 021, India
    • ,
  • Pushplata Prasad

      Affiliations

    • Department of Genetics, University of Delhi South Campus, New Delhi 110 021, India
    • ,
  • Thelma B.K.

      Affiliations

    • Department of Genetics, University of Delhi South Campus, New Delhi 110 021, India
    • Corresponding Author InformationCorresponding author. Tel.: +91 11 24118201; fax: +91 11 24112761.
    • ,
  • K.M. Prasanna Kumar

      Affiliations

    • Department of Endocrinology and Metabolism, M.S. Ramiah Medical College, Bangalore, India
    • ,
  • A.C. Ammini

      Affiliations

    • Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India
    • ,
  • Arvind Gupta

      Affiliations

    • Jaipur Diabetes Research Centre, Jaipur, India
    • ,
  • Rajeev Gupta

      Affiliations

    • Monilek Hospital and Research Centre, Jaipur, India

Received 18 April 2007; received in revised form 16 July 2007; accepted 18 October 2007. published online 14 March 2008.

No conflict of interest. This is an original research article and has not been published or under consideration in any other journal. All the authors have read through the manuscript and given consent for communication.

Abstract 

Background

There are significant regional variations in prevalence of diabetes and diabetic chronic renal insufficiency (CRI) in India. Oxidative stress plays an important role in the development of diabetic complications. To determine the importance of the polymorphisms in the genes involved in maintenance of cellular redox balance, we performed a case control study in subjects from south and north India.

Methods

Successive cases presenting to the study centers with Type 2 diabetes of >2 years duration and moderate CRI (n=194, south India 104, north India 90) diagnosed by serum creatinine ≥2 mg/dl after exclusion of nondiabetic causes of CRI were compared with diabetes subjects with no evidence of renal disease (n=224, south India 149, north India 75). Twenty-six polymorphisms from 13 genes from the oxidative stress pathway were analyzed using polymerase chain reaction–restriction fragment length polymorphism. Genes included were superoxide dismutases (SOD1, 2, 3), uncoupling proteins (UCP1, 2), endothelial nitric oxide synthase (NOS3), glutathione-S-transferases (GST) (M1, T1, P1), vascular endothelial growth factor (VEGF), paraoxonase (PON) 1 and 2, and nicotinamide adenine dinucleotide phosphate reduced, oxidase p22phox. Genes were tested for their association with CRI using χ2 test.

Results

In south Indian (SI) subjects there was significant allelic and genotypic association of the wild-type allele in SOD2 (Ala9Val; P=.002 and P=.013, respectively), UCP1 (−112 T>G, P=.012 and P=.009; Ala64Thr, P=.015 and P=.004), NOS3 (Glu298Asp, P=.002 and P=.009) and GSTP1 (Ile105Val, P=.003 and P=.004) genes with development of CRI. None of these observations were replicated in the north Indian (NI) subjects. A genotypic but not allelic association was observed for two markers, VEGF (−460 T>C) and PON1 (Arg192Gly) among NI diabetic CRI subjects.

Conclusion

The nonreplication of association suggests differential genetic susceptibility of the two populations to diabetic chronic renal insufficiency. In the SI diabetic subjects, oxidative stress pathway genes might be an important predictor for the development of diabetic complications. Further, the association of wild-type alleles may suggest that they confer greater survival ability to comorbid complications and may be nephroprotective.

Keywords: Oxidative stress, Candidate genes, Single nucleotide polymorphisms, Association, Chronic renal insufficiency, India

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☆ This study received financial assistance through senior research fellowships to Arun K. Tiwari, from University Grants Commission, New Delhi, and Pushplata Prasad, from Council of Scientific and Industrial Research, New Delhi, India.

PII: S1056-8727(07)00131-6

doi:10.1016/j.jdiacomp.2007.10.003

Journal of Diabetes and Its Complications
Volume 23, Issue 2 , Pages 102-111, March 2009

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