Association of the INS VNTR with size at birth

David B. Dunger, Ken K.L. Ong, Stewart J. Huxtable, Andrea Sherriff, Kathryn A. Woods, Marion L. Ahmed, Jean Golding, Marcus E. Pembrey, Sue Ring, Simon T. Bennett, John A. Todd

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes tn adult life. 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), 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; ALSPAC) 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 III/III genotype might have bestowed a perinatal survival during human history by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.

Original languageEnglish (US)
Pages (from-to)98-100
Number of pages3
JournalNature genetics
Issue number1
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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