title: Endothelial nitric oxide synthase gene polymorphisms and renal responsiveness to RAS inhibition therapy in type 2 diabetic Asian Indians.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Balneek Singh
authors.initials: BS
authors.lastname: Cheema
authors.forename: Harbir Singh
authors.initials: HS
authors.lastname: Kohli
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D018598:Minisatellite Repeats; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003404:Creatinine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III