title: Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese.
abstract: It was reported that gene polymorphisms in the fat-mass and obesity-associated gene (FTO) were associated with obesity and diabetes in several genome-wide association studies. A recent report indicated that FTO-knockout mice exhibited phenotypes of skinny body shape and normal metabolic profiles. Thus, FTO could be important in metabolic disorders. The aim of this study was to clarify the role of single nucleotide polymorphisms (SNPs) in FTO in metabolic disorders such as hypertension, obesity, diabetes, dyslipidemia, insulin resistance and metabolic syndrome in the Japanese general population using data from a cohort study in Hokkaido, namely the Tanno-Sobetsu study. Written informed consent for the genetic analysis was obtained from each subject participating in the study. A total of 1514 subjects were genotyped by TaqMan PCR methods for three SNPs, rs9939609, rs1121980 and rs1558902, in FTO. Association analyses between the SNPs and metabolic parameters were performed. Although two SNPs, rs9939609 and rs1558902, were not significantly associated with hypertension, obesity, metabolic syndrome or any metabolic parameters, additive and recessive models of rs1121980 were strongly associated with plasma immunoreactive insulin (IRI) level and homeostasis model assessment insulin resistance (HOMA-IR), even after adjusting for confounding factors such as age, gender and body mass index. A haplotype of three SNPs was also significantly associated with IRI and HOMA-IR. One SNP, rs1121980, and a haplotype of three SNPs in FTO that contains this SNP, might be important in the progression of insulin resistance in Japanese subjects.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Shimaoka
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohishi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akasaka
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Oguro
authors.forename: Ada
authors.initials: A
authors.lastname: Congrains
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000208:ethnology* / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human