Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population.
BACKGROUND
A genome-wide association study in the French population has detected that novel single-nucleotide polymorphisms (SNPs) in the IDE-KIF11-HHEX gene locus and the SLC30A8 gene locus are associated with susceptibility to type 2 diabetes.


OBJECTIVE
We investigated whether SNPs in these loci were associated with type 2 diabetes in Japanese.


METHODS
Two SNPs, rs7923837 and rs1111875, in the IDE-KIF11-HHEX gene locus and one SNP, rs13266634, in the SLC30A8 gene locus were genotyped in Japanese type 2 diabetic patients (n = 405) and in nondiabetic control subjects (n = 340) using the TaqMan genotyping assay system.


RESULTS
The G allele of rs7923837 was associated with type 2 diabetes [odds ratio 1.66, 95% confidence interval (CI) 1.28-2.15; P = 0.00014], following the same tendency as in the French population of the previous report. Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.57 (95% CI 1.15-2.16; P = 0.0050) and 3.16 (95% CI 1.40-7.16; P = 0.0038) relative to noncarriers. Although the G allele was a major allele (66.5%) in the French population, it was a minor allele (23.8%) in Japanese. The G allele of rs1111875 was also associated with type 2 diabetes (odds ratio 1.42, 95% CI 1.13-1.78; P = 0.0024). Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.31 (95% CI 0.97-1.77; P = 0.0810) and 2.40 (95% CI 1.34-4.32; P = 0.0028) relative to noncarriers. A significant association with type 2 diabetes was not observed for rs13266634.


CONCLUSIONS
Polymorphisms in the IDE-KIF11-HHEX gene locus are associated with susceptibility to type 2 diabetes across the boundary of race.
Furukawa
Yasushi
Y
The First Department of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Shimada
Takeshi
T
Furuta
Hiroto
H
Matsuno
Shohei
S
Kusuyama
Akiko
A
Doi
Asako
A
Nishi
Masahiro
M
Sasaki
Hideyuki
H
Sanke
Tokio
T
Nanjo
Kishio
K
D000368:Aged; D000483:Alleles; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D007564:Japan; D016547:Kinesins / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
C078492:HHEX protein, human; D018398:Homeodomain Proteins; C470243:KIF11 protein, human; D014157:Transcription Factors; D004247:DNA; D007339:Insulysin; D016547:Kinesins