Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population.
OBJECTIVE
Recently, several genes have been shown to be associated with an increased risk of type 2 diabetes by genome-wide association studies in white populations. To further investigate the involvement of these polymorphisms in conferring susceptibility to type 2 diabetes, we examined the association of 14 single nucleotide polymorphisms (SNPs) within 11 candidate loci with type 2 diabetes in a Japanese population.


METHODS
We analyzed 14 SNPs (rs4402960 in IGF2BP2, rs10811661 in CDKN2A/B, rs1111875 and rs7923837 in HHEX, rs13266634 in SLC30A8, rs1113132 and rs11037909 in EXT2, rs9939609 and rs8050136 in FTO, rs7756992 in CDKAL1, rs1801282 in PPARG Pro12Ara, rs5219 in KCNJ11 Glu23Lys, rs7480010 in LOC387761, and rs9300039 in Ch11) in 1,630 Japanese subjects with type 2 diabetes and in 1,064 control subjects by using an invader assay or a TaqMan assay.


RESULTS
Among the 11 loci examined, 6 were significantly associated with type 2 diabetes in our population by a logistic regression analysis, similar to previously reported results (rs4402960, P = 0.00009; rs10811661, P = 0.0024; rs5219, P = 0.0034; rs1111875, P = 0.0064; rs13266634, P = 0.0073; rs7756992, P = 0.0363). In this population, the remaining five loci were not significantly associated with type 2 diabetes. In addition, we identified significant association of the SNPs in FTO gene with BMI in the control subjects.


CONCLUSIONS
We have identified 6 of the 11 loci that were identified by genome-wide association studies in white populations, and these loci are considered strong candidates for type 2 diabetes susceptibility across different ethnicities.
Omori
Shintaro
S
Laboratory for Diabetic Nephropathy, SNP Research Center, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Tanaka
Yasushi
Y
Takahashi
Atsushi
A
Hirose
Hiroshi
H
Kashiwagi
Atsunori
A
Kaku
Kohei
K
Kawamori
Ryuzo
R
Nakamura
Yusuke
Y
Maeda
Shiro
S
D000368:Aged; D000483:Alleles; D044466:Asian People; D027682:Cation Transport Proteins / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D000075703:Zinc Transporter 8; D012359:tRNA Methyltransferases; D000099161:Kcnj11 Channel
D027682:Cation Transport Proteins; D051360:Cyclin-Dependent Kinase 5; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018398:Homeodomain Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D024661:Potassium Channels, Inwardly Rectifying; D014157:Transcription Factors; D000075703:Zinc Transporter 8; D012359:tRNA Methyltransferases; D000099161:Kcnj11 Channel; C078492:HHEX protein, human; C492522:SLC30A8 protein, human; C525110:CDKAL1 protein, human