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

OBJECTIVE - To investigate the frequency of variants of the glucokinas e (GCK) gene in subjects with late-onset non-insulin-dependent diabete s mellitus (NIDDM) and in subjects with late-onset impaired glucose to lerance (IGT). RESEARCH DESIGN AND METHODS - The study population incl uded 36 Finnish patients with late-onset NIDDM who were treated with d iet 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 a nd liver promotor regions of the GCK gene were amplified with the poly merase chain reaction and screened for mutations using single-strand c onformation polymorphism analysis. RESULTS - A silent third-base subst itution (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 isle t exon 1 at nucleotide 403 (C-->G) in 16.7% of NIDDM patients and in 1 7.5% 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 bas e pairs upstream from the splice acceptor site, was found in 5.6% of N IDDM 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 NIDD M or IGT in the Finnish population.