title: Replication study for the association of a single-nucleotide polymorphism, rs3746876, within KCNJ15, with susceptibility to type 2 diabetes in a Japanese population.
abstract: By an association mapping for the candidate locus in chromosome 21q, rs3746876 within KCNJ15 was shown to be associated with type 2 diabetes in Japanese populations. However, the association of rs3746876 with type 2 diabetes has not been validated in an independent cohort. The aim of the present study was to ascertain the association of rs3746876 with type 2 diabetes in an independent larger Japanese sample. We genotyped 7885 Japanese participants (4967 individuals with type 2 diabetes and 2918 control individuals) for rs3746876 with polymerase-chain reaction-invader assay. The association of rs3746876 with type 2 diabetes was examined by using logistic regression analysis. Quantitative traits analyses for homeostasis model assessment (HOMA) of β-cell function, HOMA of insulin resistance, fasting plasma glucose, fasting immunoreactive insulin and body mass index (BMI) were performed in control individuals by using multiple-linear regression analysis. We observed a significant association of rs3746876-T with type 2 diabetes (P=0.0281, odds ratio (OR)=0.82, 95% confidence interval (CI, 0.68-0.98)), but the direction of effect was opposite to that in the original report. The association of rs3746876 with type 2 diabetes was more significant in obese patients (BMI ≥ 25 kg m(-2), P=0.0025, OR=0.62, 95% CI, 0.45-0.84). We did not observe significant association of rs3746876 with any of the quantitative traits in the control individuals. We could not replicate the original finding for the association of rs3746876 with type 2 diabetes, although rs3746876 was significantly associated with obese type 2 diabetes in the present Japanese population.
authors.affiliation: Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Minako
authors.initials: M
authors.lastname: Imamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Minoru
authors.initials: M
authors.lastname: Iwata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirose
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*
chemical_list: D007328:Insulin; C103861:KCNJ15 protein, human; D024661:Potassium Channels, Inwardly Rectifying