GLUCOKINASE GENE VARIANTS IN SUBJECTS WITH LATE-ONSET NIDDM AND IMPAIRED GLUCOSE-TOLERANCE

被引:13
作者
LAAKSO, M
MALKKI, M
KEKALAINEN, P
KUUSISTO, J
MYKKANEN, L
DEEB, SS
机构
[1] UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195
[2] UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195
[3] KUOPIO UNIV HOSP,DEPT MED,SF-70210 KUOPIO,FINLAND
关键词
D O I
10.2337/diacare.18.3.398
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - To investigate the frequency of variants of the glucokinase (GCK) gene in subjects with late-onset non-insulin-dependent diabetes mellitus (NIDDM) and in subjects with late-onset impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS - The study population included 36 Finnish patients with late-onset NIDDM who were treated with diet for >8 years or who were newly diagnosed and 40 subjects with late-onset IGT who had low or normal insulin levels when tested by an oral glucose tolerance test. All exons, exon-intron junctions, and islet and liver promotor regions of the GCK gene were amplified with the polymerase chain reaction and screened for mutations using single-strand conformation polymorphism analysis. RESULTS - A silent third-base substitution (TAC-->TAT) in codon 215 of exon 6 was found in 2.8% of NIDDM patients and in 5.0% of IGT subjects. Polymorphisms were found in islet exon 1 at nucleotide 403 (C-->G) in 16.7% of NIDDM patients and in 17.5% of IGT subjects and in the noncoding region of the islet promotor at nucleotide -30 (G-->A) in 13.9% of NIDDM patients and in 25.0% of IGT subjects. Furthermore, in liver intron 1 a variant (C-->T), 12 base pairs upstream from the splice acceptor site, was found in 5.6% of NIDDM patients and in 7.5% of IGT subjects. CONCLUSIONS - These results indicate that the mutations in the coding region of the GCK gene are not likely to play a major role in the pathogenesis of late-onset NIDDM or IGT in the Finnish population.
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页码:398 / 400
页数:3
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