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- Title
Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene.
- Authors
Weedon, Michael N; Frayling, Timothy M; Shields, Beverley; Knight, Beatrice; Turner, Tina; Metcalf, Bradley S; Voss, Linda; Wilkin, Terence J; McCarthy, Anne; Ben-Shlomo, Yoav; Davey Smith, George; Ring, Sue; Jones, Richard; Golding, Jean; Byberg, Liisa; Mann, Vera; Axelsson, Tomas; Syvänen, Ann-Christine; Leon, David; Hattersley, Andrew T
- Abstract
Rare mutations in the glucokinase (GCK) gene cause fasting hyperglycemia and considerably influence birth weight when present in a mother or her offspring. The role of common variation of GCK is uncertain. A polymorphism at position -30 of the GCK beta-cell-specific promoter, present in 30% of the population, has been variably associated with type 2 diabetes and diabetes-related quantitative traits. Using 1,763 U.K. Caucasian normoglycemic adult subjects, we demonstrated that the A allele at GCK(-30) is associated with a 0.06-mmol/l increase in fasting plasma glucose (FPG) (P = 0.003). The A allele was also associated with an increase in FPG in 755 women who were 28 weeks pregnant (0.075 mmol/l, P = 0.003). We then went on to analyze the effect of GCK(-30) on birth weight using 2,689 mother/child pairs. The presence of the A allele in the mother was associated with a 64-g (25-102 g) increase in offspring birth weight (P = 0.001). We did not detect a fetal genotype effect. The increase in offspring birth weight in the 30% of mothers carrying an A allele at GCK(-30) is likely to reflect an elevated FPG during pregnancy. This study establishes that common genetic variation, in addition to rare mutations and environmental factors, can affect both FPG and birth weight.
- Publication
Diabetes, 2005, Vol 54, Issue 2, p576
- ISSN
0012-1797
- Publication type
Journal Article
- DOI
10.2337/diabetes.54.2.576