Inconsistent effects of the proline(12) -> alanine variant of the peroxisome proliferator-activated receptor-gamma 2 gene on body mass index in children and adolescent girls

Objective: To ascertain whether variation in peroxisome proliferator-activa ted receptor-gamma (PPAR-gamma), a nuclear ligand-dependent transcription f actor affecting both adipocyte differentiation and insulin sensitivity, inf luences body mass index (BMI). Design: Association study. Setting: Academic research environment. Patient(s): Children with premature pubic hair and adolescent girls with hy perandrogenism. Intervention (s): Assay for P12A and P115Q variants and measure BMI. Main Outcome Measure(s): BMI and PPAR-gamma genotypes. Result(s): Fourteen subjects were heterozygous for P12A; two were homozygou s. None carried the P115Q allele. No significant differences in BMI or basa l androstenedione concentrations between P12 carriers and noncarriers were found. Thirty-nine subjects had BMI values at two time points; mean BMI was significantly greater in the P12A carriers at time point 2. Those P12A car riers obese at time point 1 became more obese; lean mutation carriers tende d to remain lean. Annual rate of increase in BMI was significantly greater in the P12A carriers than the noncarriers. Conclusion(s): Our findings suggest that P12A may be a genetic marker indic ating risk for obesity persisting into adolescence, Future studies are need ed to determine whether the divergent effects of P12A persist into adulthoo d, to elucidate the mechanism of this effect, and to replicate our findings in other populations, (Fertil Steril(R) 2001;76:741-7. (C) 2001 by America n Society for Reproductive Medicine.).