A -30G>A polymorphism of the beta-cell-specific glucokinase promoter associates with hyperglycemia in the general population of whites.
A graded relationship has been reported between fasting and postprandial plasma glucose levels and the subsequent risk of cardiovascular morbidity and mortality. We hypothesized that the GCK -30G>A promoter polymorphism is associated with elevated glycemia in the middle-aged general population of whites, as well as with features of the World Health Organization (WHO)-defined metabolic syndrome. The GCK -30G>A polymorphism was genotyped in the population-based Inter99 study cohort (5,965 subjects) and in 332 nondiabetic subjects and 1,063 patients with type 2 diabetes. In the Inter99 cohort, the GCK -30A allele was associated with increased fasting (P < 0.001) and post-oral glucose tolerance test (OGTT) plasma glucose levels (P < 0.001), and in the same cohort, the GCK -30A allele was more frequent among 1,325 subjects with the metabolic syndrome than among 1,679 subjects without any components of the metabolic syndrome (P = 0.002). Moreover, the GCK -30A allele frequency was higher among 2,587 subjects with impaired glucose regulation (IGR) than among 4,773 glucose-tolerant subjects (17.3% [95% CI 16.2-18.3] vs. 15.0% [14.3-15.7], P < 0.001, odds ratio GG vs. GA 1.21 [1.08-1.36], GG vs. AA 1.62 [1.17-2.24]). In conclusion, the GCK -30G>A polymorphism associates with elevated fasting and post-OGTT glycemia in the middle-aged general population of whites, as well as with IGR and other features of the WHO-defined metabolic syndrome.
Rose
Christian S
CS
Steno Diabetes Center, DK-2820 Gentofte, Denmark. csro@steno.dk
Ek
Jakob
J
Urhammer
Søren A
SA
Glümer
Charlotte
C
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Pedersen
Oluf
O
Hansen
Torben
T
D000328:Adult; D000483:Alleles; D000886:Anthropometry; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D005215:Fasting; D005502:Food; D005787:Gene Frequency; D005838:Genotype; D005941:Glucokinase / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D007515:Islets of Langerhans / Q000201:enzymology*; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044465:White People / Q000235:genetics*; D014944:World Health Organization
D001786:Blood Glucose; D005941:Glucokinase