title: Common variants of GIP are associated with visceral fat accumulation in Japanese adults.
abstract: Animal studies have demonstrated that glucose-dependent insulinotropic polypeptide (GIP) and GIP receptor (GIPR) contribute to the etiology of obesity. In humans, genomewide association studies have identified single nucleotide polymorphisms (SNPs) in the GIPR gene that are strongly associated with body mass index (BMI); however, it is not clear whether genetic variations in the GIP gene are involved in the development of obesity. In the current study, we assessed the impact of GIP SNPs on obesity-related traits in Japanese adults. Six tag SNPs were tested for associations with obesity-related traits in 3,013 individuals. Multiple linear regression analyses showed that rs9904288, located at the 3'-end of GIP, was significantly associated with visceral fat area (VFA). Moreover, rs1390154 and rs4794008 showed significant associations with plasma triglyceride levels and hemoglobin A1c levels, respectively. Among the significant SNPs, rs9904288 and rs1390154 were independently linked with SNPs in active enhancers of the duodenum mucosa, the main GIP-secreting tissue. The haplotypes of these two SNPs exhibited stronger associations with VFA. Numbers of VFA-increasing alleles of rs9904288 and BMI-increasing alleles of previously identified GIPR SNPs showed a strong additive effect on VFA, waist circumference, and BMI in the subject population. These novel results support the notion that the GIP-GIPR axis plays a role in the etiology of central obesity in humans, which is characterized by the accumulation of visceral fat.
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; and nakayama@jichi.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; and.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; and.
authors.forename: Supichaya
authors.initials: S
authors.lastname: Boonvisut
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; and.
authors.forename: Saho
authors.initials: S
authors.lastname: Makishima
authors.affiliation: Jichi Medical University Health Care Center, Tochigi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyashita
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; and.
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Iwamoto
mesh_terms: D050153:Abdominal Fat / Q000502:physiology*; D000483:Alleles; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects
chemical_list: D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor
keywords: glucose-dependent insulinotropic polypeptide; glucose-dependent insulinotropic polypeptide receptor; single nucleotide polymorphism