1. Endothelial nitric oxide synthase gene polymorphisms and renal responsiveness to RAS inhibition therapy in type 2 diabetic Asian Indians
- Author
-
Cheema, Balneek Singh, kohli, Harbir Singh, Sharma, Rajni, Bhansali, Anil, and Khullar, Madhu
- Subjects
- *
ENDOTHELIAL cells , *NITRIC-oxide synthases , *GENETIC polymorphisms , *SINGLE nucleotide polymorphisms , *TYPE 2 diabetes , *DISEASES , *INDIANS (Asians) - Abstract
Abstract: Aim: To investigate the association of functional single nucleotide polymorphisms (SNPs) of the endothelial nitric oxide synthase gene (eNOS) gene (T-786C, G894T) and one variable number tandem repeat polymorphism (aa 27VNTR bb) with reno-protective response to angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy in North Indian type 2 diabetic mellitus (T2DM) subjects with cases having diabetic nephropathy (DN) and controls without DN. Method: We genotyped three polymorphisms of eNOS (two SNPs: T-786C, G894T and one 27 VNTR) in T2DM patients with overt nephropathy (cases: n =320) and T2DM patients without overt nephropathy (controls: n =490), using validated PCR-RFLP assays. These 810 North Indian T2DM patients treated with ACEI or ARB after diagnosis were followed up for 3 years. Percent changes in eGFR, urinary albumin excretion (UAE), serum creatinine at the end of 3 years of treatment were taken as end points of renoprotective response. Result: We observed that in normoalbuminuric patients, eNOS -786 CC genotype and haplotypes C-b-G and C-b-T were associated with lesser renoprotective response to ACEI. While, in macroalbuminurics, eNOS -786 CC genotype, haplotypes C-b-G and C-b-T and 27VNTR aa were associated with better renoprotective response to ACEI/ARB. Conclusion: Our results showed that eNOS T-786C CC genotype and 27VNTR individually and in interaction with other eNOS SNPs modulate renoprotective efficacy of ACEI and ARB in T2DM patients, depending on the status of proteinuria. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF