Identification of Two Missense Mutations in the GIP Receptor Gene: A Functional Study and Association Analysis with NIDDM: No Evidence of Association with Japanese NIDDM Subjects

• DOI: 10.2337/diab.45.12.1701
• Publication Date: 2013-09-19T17:42:54Z
• Authors: Akira Kubota; Yuichiro Yamada; Tadao Hayami; Koichiro Yasuda; Yoshimichi Someya; Yu Ihara; Shinji Kagimoto; Rie Watanabe; Tomohiko Taminato; Kinsuke Tsuda; Yutaka Seino
• Keywords: Gastric inhibitory polypeptide; Incretin; Single-strand conformation polymorphism

Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. Because insulinotropic effect GIP is reduced NIDDM, it should be clarified whether defects receptor gene contribute to impaired NIDDM. Using genomic DNA samples Japanese NIDDM and non-NIDDM subjects, we have investigated entire coding region by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). We identified two missense mutations, Gly198→Cys (Gly198Cys) exon 7 Glu354→Gln (Glu354Gln) 12. Investigation function with either these mutations reveals a half-maximal stimulation value GIP-induced cAMP response Chinese hamster ovary cells expressing Gly198Cys 6.3 ± 1.2 × 10−10 mol/l (n = 3), which was considerably higher than that normal receptor, 9.4 3.8 10−12 whereas Glu354Gln not significantly different receptor. To assess possible role genetic susceptibility examined allelic frequencies control subjects. Association studies show no relationship between mutations.