title: Effect of +36T>C in intron 1 on the glutamine: fructose-6-phosphate amidotransferase 1 gene and its contribution to type 2 diabetes in different populations.
abstract: Glutamine: fructose-6-phosphate amidotransferase 1 (GFPT1) acts as a rate-limiting enzyme in the hexosamine biosynthetic pathway, which is an alternative branch of glucose metabolism. To evaluate GFPT1 as a susceptibility gene to type 2 diabetes, we surveyed the polymorphisms related with the gene function of GFPT1 and assessed its contribution to type 2 diabetes with a case-control association study. Screening of the 5'-flanking and all coding regions of GFPT1 revealed eight polymorphisms, one in the 5'-flanking region, one synonymous polymorphism in exon 8, five in introns and one in 3'-UTR, but no mis-sense or non-sense polymorphism. With in silico simulation, a putative promoter region was apparently predicted between 1 kb upstream and 1 kb downstream of the start codon. In this region, +36T>C polymorphism was located on the GC box sequence in intron 1, and its functional effect on promoter activity was confirmed by luciferase reporter assay, introducing a new functional polymorphism of the GFPT1 gene. To examine its association with type 2 diabetes, we analyzed 2,763 Japanese (1,461 controls and 1,302 cases) and 330 Caucasians (190 controls and 140 cases). One possible association of +36T>C was observed in Caucasians, but no association of polymorphisms including +36T>C in intron 1 or haplotypes was observed in Japanese. Although we could not completely rule out a contribution to specific sub-groups or other populations, genetic variation of GFPT1 is unlikely to have a major role in the susceptibility to type 2 diabetes in Japanese.
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima-city, 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-city, Tokushima, 770-8503, Japan.
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Department of Human Pathology, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kudo
authors.affiliation: Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizusawa
authors.affiliation: New Industry Creation Hatchery Center, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai-city, Miyagi, 980-8579, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
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-city, Kyoto, 602-8566, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
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-city, Kyoto, 602-8566, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Yamaoka Clinic, 3-13-25, Narashinodai, Funabashi-city, Chiba, 274-0063, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaoka
authors.affiliation: Core Technology Laboratories, Sankyo Co., Limited, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yasumo
authors.affiliation: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima-city, 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-city, 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-city, 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-city, Tokushima, 770-8503, Japan. itakura@genome.tokushima-u.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D024506:5' Flanking Region; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics
chemical_list: C497511:GFPT1 protein, human; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)