1993 Fiscal Year Final Research Report Summary
Analysis of genes involved in the susceptibility to type 2 diabetes
| Project/Area Number |
03454517
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Yamaguchi University School of Medicine |
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Principal Investigator |
KAKU Kohei Yamaguchi University School of Medicine, The 3rd Department of Internal Medicine, Associate Professor, 医学部, 助教授 (10116709)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUTANI Akira Yamaguchi University School of Medicine, The 3rd Department of Internal medicine, 医学部・附属病院, 助手 (10190464)
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| Project Period (FY) |
1991 – 1993
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| Keywords | NIDDM / glucose transporter gene / glucokinase gene / genetic markers / PCR-SSCP / direct sequencing / sequence variation / promoter activity |
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| Research Abstract |
[1991]1.Study samples and DNA preparation : Genomic DNA was extracted from white blood cells of subjects with NIDDM and nondiabetic subjects (>40 yr of age, no personal history of diabetes mellitus, and a random plasma glucose of <6.7 mM).2.Glucose transporter genes in NIDDM - Population study : Contribution of GLUTI and GLUT4 genes to NIDDM was evalulated using genetic markers. A strong association between (-) allele of Xbal site in GLUTI locus and NIDDM was found, but no difference in allelic frequencies of KpnI site in GLUT4 between NIDDM and nondiabetic subjects was observed.
[1992]1.Molecular scanning of the GLUT1 gene : Sequence variations in the gene encoding GLUT1 in NIDDM subjects with (-)allele of XbaI site were qnqlyzed using PCR-SSCP and direct sequaencing. Silent mutations were detected in exon 2,5,7,9, and 10.2.Glucokinase gene in NIDDM - Population study : Allelic frequencies of two microsatelite repeat polymorphisms, GCK1 and GCK2, were analyzed. The Z+4 allele in GCK1was found more frequently in diabetic than in nondiabetic subjects, suggesting a relationship between glucokinase defects and the susceptibility to NIDDM in Japanese population.
[1993]1.Molecular scanning of the glucokinase gene : In the conding region, a silet mutation in exon 4 was identified. Sequence variations in the islet promoter(at -282, -194, and -30) and in the liver pomoter (at -258) were identified. The frequencies of the variants did not differ between NIDDM and nondiabetic subjects.2.Analysis of promoter activity of the variants in the islet promoter : To assess the effect of sequence variations in the islet promoter region on promoter activety, the promoter activity was analyzed using the luciferase expression vector transformed into HIT cells. The promoter activity of the variant (G - A at -30) was significantly lowered.
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Research Products
(11 results)
