Abstract
Size at birth is an important determinant of perinatal survival1 and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life2. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. We have tested the insulin gene (INS) variable number of tandem repeats (VNTR) locus, which in Caucasians has two main allele sizes (class I and class III; ref. 3)r as a functional candidate polymorphism for association with size at birth, as it has been shown to influence transcription of INS (refs 3–5). In a cohort of 758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC6) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birth: class III homozygotes had larger mean head circumference (P= 0.004) than class I homozygotes. These associations were amplified in babies who did not show postnatal realignment of growth (45%), and were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS VNTR Ill/Ill genotype might have bestowed a perinatal survival during human history7 by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.
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Dunger, D., Ong, K., Huxtable, S. et al. Association of the INS VNTR with size at birth. Nat Genet 19, 98–100 (1998). https://doi.org/10.1038/ng0598-98
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DOI: https://doi.org/10.1038/ng0598-98
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