alexa Five missense mutations in glucagon-like peptide 1 receptor gene in Japanese population.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Tokuyama Y, Matsui K, Egashira T, Nozaki O, Ishizuka T,

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Abstract To address the possibility that the partial disruption of Glucagon-like peptide-1 (GLP-1) signaling could cause diabetes, we tried to detect the mutation in GLP-1 receptor (GLP-1R) gene in the population with type 2 diabetes. Genomic DNA was extracted from 36 unrelated Japanese type 2 diabetic subjects and directly sequenced for the GLP-1R gene. For the detected polymorphisms, 791 patients with type 2 diabetes and 318 controls were screened by polymerase chain reaction-restricted fragment length polymorphism and association study was carried out. Five missense and four silent variants were detected in the GLP-1R gene. There were no significant differences in the frequencies of Pro7Leu, Arg44His and Leu260Pro polymorphism between the diabetic and control groups. And also there were no significant differences in body mass index (BMI), onset age and fasting IRI among the wild type, heterozygote and homozygote of these variants in diabetic patients. Thr149Met mutation was detected in one case among 791 type 2 diabetes patients, but not in control subjects. The patient with this mutation exhibited impairment of both insulin secretion, insulin sensitivity and glucose effectiveness, which may be partially explained by Thr149Met mutation in GLP-1R, though family linkage analysis and function analysis remain to be examined. This article was published in Diabetes Res Clin Pract and referenced in Journal of Clinical & Experimental Pharmacology

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