Submitted: 09 Jan 2017
Accepted: 27 Mar 2017
ePublished: 05 Apr 2017
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J Prev Epidemiol. 2017;2(1): e06.
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Insulin receptor gene polymorphisms modify the progression of kidney failure in diabetic nephropathy patients

Mookambika R. Velayuthan 1,2, Ramprasad Elumalai 1, Soundararajan Periyasamy 1, Bhaskar V.K.S. Lakkakula 3,4*

1 Department of Nephrology, Sri Ramachandra University, Chennai, India
2 Department of Medicine, Mookambika Institute of Medical Sciences, Kulasekaram, Tamil Nadu, India
3 Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India
4 Sickle Cell Institute Chhattisgarh, Raipur, India
*Corresponding Author: Correspondence to: Bhaskar V. K. S. Lakkakula, Email: lvksbhaskar@gmail.com


Introduction: Diabetic nephropathy (DN) is one of the most common causes of end-stage renal disease (ESRD). Development and progression of DN result from a combination of genetic susceptibility and metabolic and hemodynamic abnormalities. Many studies have shown that insulin resistance can also occur in the early stages of renal disease.

Objectives: The aim of the present study is to investigate the role of insulin signalling pathway gene (INSR, IRS1, IRS2 and PPARG) polymorphisms in the progression of chronic kidney disease (CKD) in diabetic patients.

Patients and Methods: A total of 9 single nucleotide polymorphisms (SNPs) were genotyped in 261 individuals with persistent urine albuminuria using fluorescence resonance energy transfer (FRET)based KASPar method. Genotypes and haplotypes were compared between early and advanced CKD groups. The effect of genotypes and glycemic control on CKD progression was assessed using univariate and multivariate logistic regression. Interaction between CKD groups and glycemic control was studied using Mantel-Haenszel (M-H)stratified analysis.

Results: Of the 9 SNPs analysed, only rs1801278 deviated Hardy-Weinberg equilibrium. The INSR rs2059807 showed decreased risk of CKD progression in non-dialysis patients and INSR rs1799817 showed heterogeneity in causing CKD progression in the absence of glycemic control. The IRS1, IRS2 and PPARG polymorphisms are not associated with the CKD progression or with uncontrolled glycemic status. Pair-wise linkage disequilibrium (LD) between SNPs of INSR or PPARG did not reveal strong LD.

Conclusion: The results of our study suggest that the INSR gene polymorphisms modify the progression of kidney failure in DN patients. Further, no significant association of CKD risk with the polymorphisms in the IRS1, IRS2 and PPARG genes was observed.

Citation: Velayuthan MR, Elumalai R, Periyasamy S, Lakkakula BVKS. Insulin receptor gene polymorphisms modify the progression of kidney failure in diabetic nephropathy patients. J Prev Epidemiol. 2017;2(1):e06.
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