title: Replication study of novel risk variants in six genes with type 2 diabetes and related quantitative traits in the Han Chinese lean individuals.
abstract: To replicating the associations of type 2 diabetes (T2D) and six novel reported variants in Han Chinese lean individuals of first episode T2D, a total of six high risk single nucleotide polymorphisms (SNPs) from the BCL11A, DUSP9, IRS1, CENTD2, ADRA2A, and CDKAL1 genes were examined. Candidate six SNPs were genotyped in 761 T2D patients and 433 control subjects, and associations between the six SNPs and Body Mass Index (BMI), Fasting Plasma Glucose (FPG) and Two Hours Oral Glucose Tolerance Test (2hOGTT) were also investigated. CDKAL1 provided the strongest evidence for replication, where rs7754840 was associated with T2D (odds ratio = 1.54, per copy of the risk C allele, P = 8.10 × 10(-7)). SNP rs5945326 at DUSP9 showed modest significance (odds ratio = 0.81, per copy of the protective G allele, P = 0.02). After adjusting the confounders of age, gender and BMI, the above results remain significant for both rs7754840 (P < 1.0 × 10(-4)) and rs5945326 (P = 0.043) respectively. After correcting for multiple testing, however, only the association between T2D and rs7754840 at CDKAL1 (P < 1×10(-4)) remains significant. In addition, the risk C allele of CDKAL1 rs7754840 was significantly associated with increased FPG levels (P = 3.8 × 10(-4)). The association between genetic variant in CDKAL1 gene was detected in the Han Chinese lean individuals. The correlation between rs7754840-C allele and increased FPG levels is consistent with the potential function of CDKAL1 gene in pancreatic islets.
authors.affiliation: Laboratory of Disorder Genes, Department of Pharmacology, College of Pharmacy, Chongqing Medical University, PO Box 380, 1 Yi Xue Yuan Road, Chongqing 400016, People's Republic of China.
authors.forename: Xiao Yun
authors.initials: XY
authors.lastname: Bao
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
authors.forename: Mao Sheng
authors.initials: MS
authors.lastname: Yang
mesh_terms: D000367:Age Factors; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics; D002681:China / Q000453:epidemiology; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D012097:Repressor Proteins; D012307:Risk Factors; D012737:Sex Factors; D013851:Thinness / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: C547768:ADRA2A protein, human; C446513:ARAP1 protein, human; C486563:BCL11A protein, human; D001786:Blood Glucose; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D009687:Nuclear Proteins; D018341:Receptors, Adrenergic, alpha-2; D012097:Repressor Proteins; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; C104821:DUSP9 protein, human; D054637:Dual-Specificity Phosphatases