Diabetes Care, Vol 18, Issue 3 398-400, Copyright © 1995 by American Diabetes Association

ARTICLES

Glucokinase gene variants in subjects with late-onset NIDDM and impaired glucose tolerance

M Laakso, M Malkki, P Kekalainen, J Kuusisto, L Mykkanen and SS Deeb
Department of Genetics, University of Washington, Seattle, USA.

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 the pathogenesis of late-onset NIDDM or IGT in the Finnish population.
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