Abstract
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×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.
Acknowledgements
This work was supported by grants from the Accredo Foundation, the Children's Foundation Research Center of Memphis at Le Bonheur Children's Medical Center, and the University of Massachusetts-Baystate Medical Center Collaborative. Additional funds were provided by the University of Tennessee Health Science Center General Clinical Research Center (grant number M01-RR00211) and the Center of Genomics and Bioinformatics at the University of Tennessee Health Science Center. We thank Dr. Kim Fisher, Sandy Grimes, and Taurus Rogers for recruiting subjects in Memphis, and Jeanette Peeples for her technical work. Additionally, we would like to thank Laura Bufkin and Kedra Wallace for their work with clinical recruitment and laboratory assistance, respectively, in Jackson.