title: Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population.
abstract: Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the genetic variants might be used as molecular markers for evaluating the risk of T2DM and diabetic nephropathy. © 2016 IUBMB Life, 68(7):516-525, 2016.
authors.affiliation: Department of Toxicology, XiangYa School of Public Health, Central South University, Changsha, Hunan, China.|Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.|Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Li
authors.affiliation: Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors.forename: Lin-Qing
authors.initials: LQ
authors.lastname: Yang
authors.affiliation: Department of Toxicology, XiangYa School of Public Health, Central South University, Changsha, Hunan, China.
authors.forename: Cai-Gao
authors.initials: CG
authors.lastname: Zhong
authors.affiliation: Department of Toxicology, XiangYa School of Public Health, Central South University, Changsha, Hunan, China.|Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Zhuang
mesh_terms: D000328:Adult; D000368:Aged; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D012307:Risk Factors
chemical_list: C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
keywords: diabetic nephropathy; nitric oxide synthase; polymorphism; type 2 diabetes mellitus