title: Common coding variant in the TCF7L2 gene and study of the association with type 2 diabetes in Japanese subjects.
abstract: Genetic variants of the transcription factor 7-like 2 (TCF7L2) gene affect the risk of type 2 diabetes in populations with multiple ethnic groups. However, a comprehensive survey of this gene has not been done for a Japanese population. Thus, we conducted this gene-based association study, in which the common genetic variants were analyzed. Using 24 Japanese type 2 diabetic subjects, we first screened a 9.5 kb region, which included the entire coding sequence, to assess potential functional variants of TCF7L2. Sequencing revealed a common coding variant (Pro477Thr) in exon 14 of TCF7L2 that was not enrolled in the public SNP database. Nineteen SNPs and the microsatellite DG10S478 were genotyped across the gene in 2,877 unrelated Japanese subjects. This independent screen identified the previously reported rs7903146 with a strongest association (allele P = 0.0001, odds ratio = 1.59 [95% confidence interval 1.25-2.01]), but there was no significant association between Pro477Thr and type 2 diabetes (allele P = 0.64). Expression of the Pro477Thr variant did not alter TCF7L2 expression in 30 lymphoblast cells. Although a genotypic effect of Pro477Thr on expression of TCF7L2 was not apparent, Pro477Thr was identified as a common variant of TCF7L2 in 2,877 Japanese subjects. Further functional studies are required to determine the possible effect of this coding variant on type 2 diabetes.
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kunika
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Department of Psychiatry, Institute of Health Biosciences, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.affiliation: Department of Psychiatry, Institute of Health Biosciences, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.|Department of Community and Psychiatric Nursing, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Shu-Ichi
authors.initials: SI
authors.lastname: Ueno
authors.affiliation: Department of Psychiatry, Institute of Health Biosciences, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, 465, Kajii-cho, Hirokoji-Kawaramachi, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Tsugawa
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miyawaki
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Moritani
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. itakura@genome.tokushima-u.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003062:Codon; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D003062:Codon; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein