title: Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.
abstract: BACKGROUND
  Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort.
  
  
  RESULTS
  Selected type 2 diabetes-associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P<or=0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8*10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1*10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3 * 10(-3). Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033).
  
  
  CONCLUSIONS
  We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities.
authors.affiliation: Department of Endocrinology, Shanghai Medical College Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.forename: Tina
authors.initials: T
authors.lastname: Rönn
authors.forename: Anders
authors.initials: A
authors.lastname: Olsson
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Yieping
authors.initials: Y
authors.lastname: Du
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Renming
authors.initials: R
authors.lastname: Hu
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D002681:China; D015331:Cohort Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D012359:tRNA Methyltransferases
chemical_list: D001786:Blood Glucose; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human