Inconsistent effects of the proline12 --> alanine variant of the peroxisome proliferator-activated receptor-gamma2 gene on body mass index in children and adolescent girls.
OBJECTIVE
To ascertain whether variation in peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear ligand-dependent transcription factor affecting both adipocyte differentiation and insulin sensitivity, influences body mass index (BMI).


METHODS
Association study.


METHODS
Academic research environment.


METHODS
Children with premature pubic hair and adolescent girls with hyperandrogenism.


METHODS
Assay for P12A and P115Q variants and measure BMI.


METHODS
BMI and PPAR-gamma genotypes.


RESULTS
Fourteen subjects were heterozygous for P12A; two were homozygous. None carried the P115Q allele. No significant differences in BMI or basal 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 carriers obese at time point 1 became more obese; lean mutation carriers tended to remain lean. Annual rate of increase in BMI was significantly greater in the P12A carriers than the noncarriers.


CONCLUSIONS
Our findings suggest that P12A may be a genetic marker indicating risk for obesity persisting into adolescence. Future studies are needed to determine whether the divergent effects of P12A persist into adulthood, to elucidate the mechanism of this effect, and to replicate our findings in other populations.
Witchel
S F
SF
Division of Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania 15213, USA. witches@chplink.chp.edu
White
C
C
Siegel
M E
ME
Aston
C E
CE
D000595:Amino Acid Sequence / Q000235:genetics; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics / Q000473:pathology; D008297:Male; D009765:Obesity / Q000235:genetics / Q000473:pathology; D011629:Puberty, Precocious / Q000235:genetics / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors