title: Identification of gene variants in NOS3, ET-1 and RAS that confer risk and protection against microangiopathy in type 2 diabetic obese subjects.
abstract: The study aim was to investigate NOS3 VNTR, NOS3 G894T, EDN1 C8002T, ACE I/D, AGT M235T and AGTR1 A1166C in nonobese and obese T2DM patients, and their interaction with the incidence of microangiopathy. T2DM subjects (n=250; 166 nonobese, and 84 obese) were genotyped for the gene variants by PCR/RFLP. The interaction of these polymorphisms with obesity and their contribution to microangiopathy were analyzed by multivariate regression analysis. A higher frequency of NOS3 4a allele was found in obese (P=0.027) vs. nonobese subjects. ACE D (P=0.009) and AGT 235T (P=0.026) alleles were associated with the reduced risk of diabetic nephropathy in nonobese and obese patients, respectively. In obese subjects, NOS3 4a (P=0.011) had a converse effect to NOS3 894T (P=0.043), and EDN1 8002T (P=0.035) on the prevalence of combined microangiopathy (neuropathy/retinopathy/nephropathy) vs. microangiopathy-negative subjects. The study indicates association of RAS variants with obesity and nephropathy, and an opposite effect of NOS3 VNTR and NOS3 G894T on the occurrence of combined microangiopathy.
authors.affiliation: Institute of Cellular Biology and Pathology N. Simionescu, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania. simona.manea@icbp.ro
authors.forename: Simona-Adriana
authors.initials: SA
authors.lastname: Manea
authors.forename: Alexandra
authors.initials: A
authors.lastname: Robciuc
authors.forename: Cristian
authors.initials: C
authors.lastname: Guja
authors.forename: Constantina
authors.initials: C
authors.lastname: Heltianu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009765:Obesity / Q000150:complications*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: C544065:AGTR1 protein, human; D019332:Endothelin-1; D044140:Receptor, Angiotensin, Type 1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D018631:ras Proteins