Glucokinase Gene Polymorphisms: a Genetic Marker for Glucose Intolerance in a Cohort of Elderly Finnish Men

Abstract

Although mutations in the glucokinase gene are implicated in the pathogenesis of glucose intolerance in pedigrees with maturity‐onset diabetes of the young, the role of such mutations in typical Type 2 diabetes is poorly characterized. We studied a cohort of elderly men born (between 1900 and 1919) in two Finnish communities and exhibiting a continuous spectrum of glucose tolerance at assessments made in 1984 and 1989. Individuals were typed at two polymorphic microsatellites straddling the glucokinase gene, GCK(3’) (n = 169) and GCK(5’) (n = 166): these two markers were in linkage equilibrium in this cohort. Significant associations between alleles at the GCK(3’) marker and glucose tolerance were evident (p = 0.002), the frequency of the (z + 2) allele rising from zero in control subjects (n = 88 chromosomes) to 6.5 % (n = 62) in subjects with impaired tolerance and 12.2 % (n = 188) in subjects with diabetes. Mean 2‐h glucose levels were 10.5 (9.6–11.4, 95 % confidence interval) mmol I‐1 in individuals with the (z + 2) allele and 8.1 (7.6–8.7) mmol I‐1 in those without (p = 0.01, corrected for multiple comparisons). No association was evident between GCK(5’) alleles and glucose tolerance. The GCK(3’) microsatellite is a marker for abnormal glucose tolerance in this cohort of elderly Finnish men. 1994 Diabetes UK