Objective: To test the association between size for gestational age and either individual polymorphisms or haplotypes of the insulin and IGF2 genes in newborns and their mothers, as well as the effect of the parental origin of haplotypes.

Subjects: 207 pairs of healthy African-American full-term newborns and mothers were recruited from Memphis TN and Jackson MS with birth weights ranging from 2210g to 4735g.

Methods: Six single nucleotide polymorphisms (SNPs) located in the insulin (INS) and insulin-like growth factor 2 (IGF2) genes were genotyped in all mothers and newborns. Associations of individual SNPs and inferred haplotypes in the newborns and mothers with size for gestational age were tested using linear regression with incorporation of significant covariables. Differences in the mean size for gestational age among newborns classified according to the parental origin of insulin haplotypes were tested by ANOVA.

Results: In newborns three INS SNPs as well as maternal BMI exhibited significant (p<0.01) association with size for gestational age, but no maternal polymorphisms were significantly associated with newborn size. For the three haplotypes with frequencies > 5% inferred from these three SNPs, there was a significant (p=0.006) difference in mean newborn size among paternally inherited haplotypes but not among maternally inherited haplotypes.

Conclusion: Newborn genotypes for polymorphisms near the 5’ end of the insulin gene are significantly associated with size for gestational age with a major effect due to the paternally inherited allele, which is preferentially expressed due to imprinting.