Genetic variations within the insulin gene region are associated with accelerated fetal growth

Size at birth has been proposed to be associated with the risk of type 2 diabetes and cardiovascular disease later in life. It is, however, unclear whether this association is attributed to an unfavorable intrauterine environment or to specific genotypes predisposing both altered fetal growth and common diseases in adult life. The aim of this study was to investigate the associations between the neonatal birth size and the genotypes of polymorphic loci within the insulin gene (INS) region, which is susceptible to diabetes mellitus. We analyzed the genotypes of two polymorphic loci; -23HphI and HUMTH01, in 520 pairs of normal Japanese mothers and their neonates, and compared with the somatoscopic characteristics at birth converted into standard deviation scores (SDS) according to sex, parity and gestational weeks at delivery. It was revealed that neonatal -23HphI T allele and HUMTH01 allele10, which are linked to the INS variable number of tandem repeats (VNTR) class III allele, were associated with increased weight, head circumstance, and length at birth. These associations confirmed that variation within the INS region, most probably at the INS-VNTR, influences fetal growth. Furthermore, the finding that the paternally transmitted -23HphI T allele was exclusively correlated with increased size at birth indicates the involvement of an imprinting mechanism. In conclusion, the INS-VNTR class III allele might accelerate fetal growth in a parent-specific manner.