ASSOCIATION OF THE INS VNTR WITH SIZE AT BIRTH

Size at birth is an important determinant of perinatal survival(1) and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life(2). Common genetic variation that regul ates fetal growth could therefore influence perinatal survival and pre dispose to the development of adult disease. We have tested the insuli n 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 bi rth, as it has been shown to influence transcription of INS (refs 3-5) . In a cohort of 758 term singletons (Avon Longitudinal Study of Pregn ancy and Childhood; ALSPAC(6)) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birt h: 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 VN TR III/III genotype might have bestowed a perinatal survival during hu man history(7) by conferring larger size at birth. Common genetic vari ation of this kind may contribute to reported associations between bir th size and adult disease.