Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children.

Variations in the perilipin () gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in , and rs35568725 in , were analyzed by RT-PCR in 1264 children aged 6-8 years. Our results showed a contrasting association of rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in and with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the SNPs with these variables.