Determinants of plasma Leptin and age at menarche in adolescent girls in Hawaii

Abstract

This study investigates the association of the Leptin (LEP) and Leptin receptor (LEPR) polymorphisms LEP A19G, LEP G-2548A and LEPR Q223R with plasma leptin concentration, body fat and age at menarche (AAM). The study was part of a larger cohort study that followed 349 multiethnic adolescent girls (ages 9-14yr at baseline) and an additional 180 girls at exam 3 in Hawaii (Female Adolescent Maturation Study). Anthropometry was obtained by measurement, Tanner stages by clinical examination, dietary intake by 3-day diet record and physical activity by a standardized questionnaire. DNA was obtained from mouthwash or blood and was genotyped using a fluorescent 5' endonuclease assay and the ABI FAST 7900HT Real-Time PCR System for allelic discrimination. Dual energy X ray Absorptiometry (DXA) was used to determine body fat mass. The study did not show association between LEP/LEPR variants and plasma leptin. However, the association between plasma leptin and body fat measures (measured using both DXA and anthropometry) was substantiated. A difference in LEPR rare homozygote genotype (AA) and the common homozygote genotype (GG) in DXA trunkto-periphery fat ratio (TPFR) was found (girls with LEPR Q223R AA genotype had lower TPFR compared to GG). It was also found that protein intake (adjusted for BMI) was negatively associated with plasma leptin level. In a COX regression model, girls with AG genotype for LEP G-2548A reached menarche earlier than the AA genotype. The study also substantiated the evidence of heavier and taller girls reaching menarche early. Importantly, this study demonstrated these associations in understudied girls of Asian White ancestry. This present study provides new information on the LEP/LEPR genetic variants, body fat and age at menarche in an Asian White population.