Objective: Circulating leptin levels positively correlate with adult BMI and size at birth. Previous studies found gender-specific associations between polymorphisms in the leptin gene and postnatal obesity-related traits or circulating leptin levels. We examined the relationships among leptin gene polymorphisms, size for gestational age, umbilical cord leptin, and gender.
Methods: Six single nucleotide polymorphisms (SNPs) were genotyped in the leptin gene in 261 newborns (72 low birth weight Caucasians, 189 randomly-selected African-Americans). In African-Americans, umbilical cord leptin and free testosterone levels were measured. Linear regression was used to identify significant predictors of size for gestational age or cord leptin levels and gender x genotype interaction effects.
Results: There is a significant interaction between gender and genotype at site -2548 (A/G). Among low birth weight Caucasians, the A allele was associated with an increase in female size for gestational age, while the A allele was associated with decreased male birth size. Among African-Americans, the A allele was associated with a decrease in umbilical cord leptin in females and with an increase in cord leptin in males. Cord testosterone levels were not a significant predictor of cord leptin levels either among all African-American newborns or among strata of -2548 genotypes and gender.
Conclusion: In male and female fetuses, site -2548 of the leptin gene may differently affect the expression level of the leptin gene or the rate of fetal growth. This gender-specific effect does not appear to be mediated by the level of free testosterone at delivery.