This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tobias, J. H. Articles by Brown, M. A. Search for Related Content PubMed PubMed Citation Articles by Tobias, J. H. Articles by Brown, M. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene SNP UniGene Related Collections Pediatric Endocrinology Female Endocrinology

Effect of an Estrogen Receptor- Intron 4 Polymorphism on Fat Mass in 11-Year-Old Children

J. H. Tobias, C. D. Steer, C. Vilario-Güell and M. A. Brown

Clinical Science at South Bristol (J.H.T.), Community Medicine (C.D.S.), University of Bristol, Bristol BS2 8HW, United Kingdom; Botnar Research Centre (C.V.-G., M.A.B.), University of Oxford, Oxford OX1 3QX, United Kingdom; and Centre for Immunology and Cancer Research (M.A.B.), University of Queensland, Brisbane QLD 4072, Australia

Address all correspondence and requests for reprints to: Dr. J. Tobias, Rheumatology Unit, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom. E-mail: jon.tobias{at}bristol.ac.uk.

Context: Polymorphisms in the ESR1 gene encoding estrogen receptor (ER)- may be associated with fat mass in adults.

Objectives: The objective of the study was to establish whether ESR1 polymorphisms influence fat mass in childhood.

Design: This was a cross-sectional analysis after genotyping of rs9340799, rs2234693, and rs7757956 ESR1 polymorphisms.

Setting: The Avon Longitudinal Study of Parents and Children (ALSPAC) was a population-based prospective study.

Participants: Participants included 3097 11-yr-old children with results for ESR1 genotyping, puberty measures, and dual-energy x-ray absorptiometry results.

Outcomes: Relationships between ESR1 polymorphisms and indices of body composition were measured.

Results: The rs7757956 polymorphism was associated with fat mass (P = 0.002). Total body fat mass (adjusted for height) was reduced by 6% in children with TA/AA genotypes, and risk of being overweight (85th centile of fat mass) was decreased by 20%. This genetic effect appeared to interact with puberty in girls (P = 0.05 for interaction): in those with the TT genotype, total body fat mass (adjusted for height) was 18% higher in Tanner stages 3–5 vs. stages 1–2; the equivalent difference was 7% in those with TA/AA genotypes. Furthermore, the risk of being overweight was 36% lower in girls with TA/AA genotypes in Tanner stages 3–5, but no reduction was seen in those in stages 1–2. Neither rs9340799 nor rs2234693 polymorphisms were associated with body composition measures.

Conclusions: Fat mass in 11-yr-old children was related to the rs7757956 ESR1 polymorphism. This association was strongest in girls in more advanced puberty, in whom the risk of being overweight was reduced by 36% in those with the TA/AA genotype.