Type 2 diabetes risk alleles are associated with reduced size at birth
Date
2009
Authors
Freathy, R.M.
Bennett, A.J.
Ring, S.M.
Shields, B.
Hypponen, E.
Hattersley, A.T.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Diabetes, 2009; 58(6):1428-1433
Statement of Responsibility
Conference Name
Abstract
Objective: Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type2 diabetes also reduce birth weight.
Research and design methods: We genotyped singlenucleotidepolymorphisms (SNPs) at five recently identified type2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2,and SLC30A8) in 7,986 mothers and 19,200 offspring from fourstudies of white Europeans. We tested the association betweenmaternal or fetal genotype at each locus and birth weight of theoffspring
Results: We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11–31], P = 2 × 10−5, and 14 g [4–23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39–120) lighter at birth than the 8% carrying none (Ptrend = 5 × 10−7). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus.
Conclusions: Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype.
School/Discipline
Dissertation Note
Provenance
Description
Link to a related website: http://diabetes.diabetesjournals.org/content/58/6/1428.full.pdf, Open Access via Unpaywall
Access Status
Rights
Copyright 2009 American Diabetes Association.