title: Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan.
abstract: 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.
authors.affiliation: Department of Diabetes and Endocrinology, Division of Molecule and Structure, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyake
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Mayumi
authors.initials: M
authors.lastname: Enya
authors.forename: Yushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hinokio
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: 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
chemical_list: 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