PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.
BACKGROUND
Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism.


RESULTS
Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006).


CONCLUSIONS
The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively.
Hu
Cheng
C
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Zhang
Rong
R
Wang
Congrong
C
Wang
Jie
J
Ma
Xiaojing
X
Lu
Jingyi
J
Qin
Wen
W
Hou
Xuhong
X
Wang
Chen
C
Bao
Yuqian
Y
Xiang
Kunsan
K
Jia
Weiping
W
D000368:Aged; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D002681:China; D051360:Cyclin-Dependent Kinase 5 / Q000096:biosynthesis*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007339:Insulysin / Q000096:biosynthesis*; D016547:Kinesins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000096:biosynthesis*; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D000075703:Zinc Transporter 8; D012359:tRNA Methyltransferases; D000099161:Kcnj11 Channel
D027682:Cation Transport Proteins; D051360:Cyclin-Dependent Kinase 5; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018398:Homeodomain Proteins; D007339:Insulysin; D016547:Kinesins; D047495:PPAR gamma; D024661:Potassium Channels, Inwardly Rectifying; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000075703:Zinc Transporter 8; D012359:tRNA Methyltransferases; D000099161:Kcnj11 Channel; C493966:CDKN2B protein, human; C078492:HHEX protein, human; C498779:IGF2BP2 protein, human; C470243:KIF11 protein, human; C492522:SLC30A8 protein, human; C525110:CDKAL1 protein, human