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.

Abstract	Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). We have identified two missense mutations, Gly198-->Cys (Gly198Cys) in exon 7 and Glu354-->Gln (Glu354Gln) in exon 12. Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. Association studies show no relationship between NIDDM and either of the two mutations.
Authors	A Kubota, Y Yamada, T Hayami, K Yasuda, Y Someya, Y Ihara, S Kagimoto, R Watanabe, T Taminato, K Tsuda, Y Seino
Journal	Diabetes (Diabetes) Vol. 45 Issue 12 Pg. 1701-5 (Dec 1996) ISSN: 0012-1797 [Print] United States
PMID	8922354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA Primers Insulin Receptors, Gastrointestinal Hormone Gastric Inhibitory Polypeptide gastric inhibitory polypeptide receptor Cyclic AMP
Topics	Alleles Animals CHO Cells Cricetinae Cyclic AMP (metabolism) DNA Mutational Analysis DNA Primers Diabetes Mellitus, Type 2 (genetics) Gastric Inhibitory Polypeptide (pharmacology) Humans Insulin (metabolism) Insulin Secretion Japan Mutation Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational Receptors, Gastrointestinal Hormone (genetics, physiology) Structure-Activity Relationship

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