Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan.
BACKGROUND
In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates.


OBJECTIVE
The aim of this study was to replicate in a Japanese population previously identified associations of single nucleotide polymorphisms (SNPs) within 10 candidate loci with type 2 diabetes using a relatively large sample size: 1921 subjects with type 2 diabetes and 1622 normal controls.


RESULTS
A total of 15 SNPs were genotyped. Eight SNPs in five loci were found to be associated with type 2 diabetes: rs3802177 [odds ratio (OR) = 1.16 (95% confidence interval (CI) 1.05-1.27); P = 4.5 x 10(-3)] in SLC30A8; rs1111875 [OR = 1.27 (95% CI 1.14-1.40); P = 1.4 x 10(-5)] and rs7923837 [OR = 1.27 (95% CI 1.13-1.43); P = 1.0 x 10(-4)] in HHEX; rs10811661 [OR = 1.27 (95% CI 1.15-1.40); P = 1.9 x 10(-6)] in CDKN2B; rs4402960 [OR = 1.23 (95% CI 1.11-1.36); P = 8.1 x 10(-5)] and rs1470579 [OR = 1.18 (95% CI 1.07-1.31); P = 8.3 x 10(-4)] in IGF2BP2; and rs7754840 [OR = 1.28 (95% CI 1.17-1.41); P = 4.5 x 10(-7)] and rs7756992 [OR = 1.27 (95% CI 1.15-1.40); P = 9.8 x 10(-7)] in CDKAL1. The first and second strongest associations were found at variants in CDKAL1 and CDKN2B, both of which are involved in the regenerative capacity of pancreatic beta-cells.


CONCLUSIONS
Some of these variants represent common type 2 diabetes-susceptibility genes in both Japanese and Europeans.
Horikawa
Yukio
Y
Department of Diabetes and Endocrinology, Division of Molecule and Structure, Gifu University School of Medicine, Gifu, Japan.
Miyake
Kazuaki
K
Yasuda
Kazuki
K
Enya
Mayumi
M
Hirota
Yushi
Y
Yamagata
Kazuya
K
Hinokio
Yoshinori
Y
Oka
Yoshitomo
Y
Iwasaki
Naoko
N
Iwamoto
Yasuhiko
Y
Yamada
Yuichiro
Y
Seino
Yutaka
Y
Maegawa
Hiroshi
H
Kashiwagi
Atsunori
A
Yamamoto
Ken
K
Tokunaga
Katsushi
K
Takeda
Jun
J
Kasuga
Masato
M
D015992:Body Mass Index; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D012359:tRNA Methyltransferases
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018971:Insulin-Like Growth Factor Binding Protein 2; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human