Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene.


Weedon, MN; Frayling, TM; Shields, B; Knight, B; Turner, T; Metcalf, BS; Voss, L; Wilkin, TJ; McCarthy, A; Ben-Shlomo, Y; Davey Smith, G; Ring, S; Jones, R; Golding, J; Byberg, L; Mann, V; Axelsson, T; Syvanen, AC; Leon, D; Hattersley, AT; (2005) Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene. Diabetes, 54 (2). pp. 576-81. ISSN 0012-1797 DOI: https://doi.org/10.2337/diabetes.54.2.576

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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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Medical Statistics
Research Centre: Centre for Maternal, Reproductive and Child Health (MARCH)
Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 15677518
Web of Science ID: 226613400034
URI: http://researchonline.lshtm.ac.uk/id/eprint/13723

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