A -30G>A polymorphism of the beta-cell-specific glucokinase promoter associates with hyperglycemia in the general population of whites

TY - JOUR

T1 - A -30G>A polymorphism of the beta-cell-specific glucokinase promoter associates with hyperglycemia in the general population of whites

AU - Rose, Christian S

AU - Ek, Jakob

AU - Urhammer, Søren A

AU - Glümer, Charlotte

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Adult

KW - Alleles

KW - Anthropometry

KW - Blood Glucose

KW - Case-Control Studies

KW - European Continental Ancestry Group

KW - Fasting

KW - Food

KW - Gene Frequency

KW - Genotype

KW - Glucokinase

KW - Glucose Tolerance Test

KW - Humans

KW - Hyperglycemia

KW - Islets of Langerhans

KW - Metabolic Syndrome X

KW - Middle Aged

KW - Polymorphism, Genetic

KW - Promoter Regions, Genetic

KW - World Health Organization

M3 - Journal article

C2 - 16186409

SN - 0012-1797

VL - 54

SP - 3026

EP - 3031

JO - Diabetes

JF - Diabetes

IS - 10

ER -