title: Association study of a common variant near IRS1 with type 2 diabetes mellitus in Chinese Han population.
abstract: The insulin receptor substrate-1 (IRS1) plays an important role in insulin signaling. A recent genome-wide association study identified rs2943641C>T as a susceptibility locus for type 2 diabetes mellitus (T2DM) in Caucasian patients. Therefore, we determined whether this common variant near IRS1 is also associated with the risk of T2DM and T2DM-related phenotypes in a Chinese Han population. A total of 2,290 unrelated Chinese Han individuals residing in Beijing were recruited in this study, including 1177 T2DM patients and 1113 subjects with normal glucose tolerance (control group). The single nucleotide polymorphism (SNP) was genotyped using a MassARRAY iPLEX system. The frequency of risk allele C was 0.929 in the control group and 0.939 in patients with T2DM. We found no association between the C allele of rs2943641 and T2DM in a recessive model [OR 1.14, 95 % confidence interval (CI) 0.89-1.45, P = 0.298], or after adjusting for sex, age, and body mass index (BMI) (OR 1.10, 95 % CI 0.85-1.43, P = 0.301). Analysis of the clinical features of the control subjects with normal glucose tolerance revealed that the 30-min plasma glucose level during a 75-g oral glucose tolerance test was significantly different between the CC and CT+TT genotypes (P = 0.017). Linear regression analysis showed that the 30-min plasma glucose levels was significantly and positively associated with the CC genotype after adjusting for sex, age, and BMI (β = 0.065, 95 % CI 0.009-0.654, P = 0.044). In addition, a potential association between this SNP and increased waist circumference (β = 1.337, 95 % CI -0.179 to 2.853, P = 0.084) was observed with adjustment for the sex and age. Our study was not able to demonstrate the association between rs2943641 near IRS1 and T2DM in a Chinese Han population. However, this SNP may be associated with postprandial hyperglycemia.
authors.affiliation: Department of Endocrinology and Metabolism, Peking University People's Hospital, No 11, Xizhimen South Street, Beijing, 100044, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Xueyao
authors.initials: X
authors.lastname: Han
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Sun
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Wulan
authors.initials: W
authors.lastname: Guo
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Yingying
authors.initials: Y
authors.lastname: Luo
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhang
authors.forename: Xianghai
authors.initials: X
authors.lastname: Zhou
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
mesh_terms: D024509:3' Flanking Region; D000368:Aged; D044466:Asian People; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D014504:Urban Health / Q000208:ethnology; D055105:Waist Circumference
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins