This Article Full Text Full Text (PDF) Submit a related Letter to the Editor 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Fox, C. S. Articles by Shearman, A. M. Search for Related Content PubMed PubMed Citation Articles by Fox, C. S. Articles by Shearman, A. M. Related Collections Cardiovascular Endocrinology Female Endocrinology Male Endocrinology Obesity

Sex-Specific Association between Estrogen Receptor- Gene Variation and Measures of Adiposity: The Framingham Heart Study

National Heart, Lung, and Blood Institute’s Framingham Heart Study (C.S.F., J.M.M., D.L.), Framingham, Massachusetts 01702; Department of Endocrinology, Diabetes, and Hypertension (C.S.F.), the Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115; Department of Biostatistics (Q.Y., L.A.C., C.-Y.G., L.D.A.), School of Public Health, Boston University, Boston, Massachusetts 02118; Department of Neurology (Q.Y., L.D.A.) and Section of General Internal Medicine (J.M.M.), Boston University School of Medicine (D.L.), Boston, Massachusetts 02118; Center for Cancer Research (D.E.H., A.M.S.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Department of Medicine (M.E.M.), Molecular Cardiology Research Institute, Tufts-New England Medical Center and Tufts-New England Medical Center Specialized Center of Research in Ischemic Heart Disease, Boston, Massachusetts 02111; and the National Heart, Lung, and Blood Institute (C.S.F., D.L.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Caroline S. Fox, M.D., M.P.H., 73 Mount Wayte Avenue, Suite 2, Framingham, Massachusetts 01702. E-mail: foxca{at}nhlbi.nih.gov.

Background: Polymorphisms in estrogen receptor- (ESR1) may be associated with variation in body mass index and waist circumference. However, most prior studies have been limited by sample size and power.

Methods: DNA from 1763 unrelated men and women (mean age, 56 yr) from the Framingham Heart Study offspring cohort was genotyped for four ESR1 polymorphisms: T30C (rs2077647) in exon 1, PvuII (rs2234693), and XbaI (rs 9340799) in intron 1, and C1335G (rs 1801132) in exon 4.

Results: Men homozygous for the PvuII C allele (frequency, 0.45) had lower waist circumference (99.3 cm), compared with TT homozygous men (99.8 cm) and heterozygotes (100.6 cm) (P < 0.004). Similar results were obtained with XbaI, which lies in the same linkage disequilibrium block. C1335G also demonstrated a gender-specific association: men with CG or GG genotypes had lower mean body mass index, 27.7 and 27.9 kg/m², respectively, compared with 28.6 kg/m² among the CC homozygotes (P < 0.01). No significant associations were seen with T30C, nor were associations observed among women.

Conclusions: Polymorphisms in ESR1 are associated with measures of adiposity in men. These associations further support the hypothesis that the intron 1 region of ESR1 influences phenotypes important for cardiovascular risk.

This article has been cited by other articles:

				C. S. Weickert, A. L. Miranda-Angulo, J. Wong, W. R. Perlman, S. E. Ward, V. Radhakrishna, R. E. Straub, D. R. Weinberger, and J. E. Kleinman Variants in the estrogen receptor alpha gene and its mRNA contribute to risk for schizophrenia Hum. Mol. Genet., August 1, 2008; 17(15): 2293 - 2309. [Abstract] [Full Text] [PDF]

				I. Peter, A. Kelley-Hedgepeth, C. S. Fox, L. Adrienne Cupples, G. S. Huggins, D. E. Housman, R. H. Karas, M. E. Mendelsohn, D. Levy, and J. M. Murabito Variation in Estrogen-Related Genes Associated with Cardiovascular Phenotypes and Circulating Estradiol, Testosterone, and Dehydroepiandrosterone Sulfate Levels J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2779 - 2785. [Abstract] [Full Text] [PDF]

				S. Kato, B. Lindholm, J. Axelsson, R. A. Qureshi, P. Barany, O. Heimburger, J.-A. Gustafsson, P. Stenvinkel, and L. Nordfors Association between oestrogen receptor {alpha} gene polymorphism and mortality in female end-stage renal disease patients Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2571 - 2577. [Abstract] [Full Text] [PDF]

				C. J. Gallagher, C. D. Langefeld, C. J. Gordon, J. K. Campbell, J. C. Mychalecky, M. Bryer-Ash, S. S. Rich, D. W. Bowden, and M. M. Sale Association of the Estrogen Receptor-{alpha} Gene With the Metabolic Syndrome and Its Component Traits in African-American Families: The Insulin Resistance Atherosclerosis Family Study Diabetes, August 1, 2007; 56(8): 2135 - 2141. [Abstract] [Full Text] [PDF]

				E. Murphy and C. Steenbergen Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury Cardiovasc Res, August 1, 2007; 75(3): 478 - 486. [Abstract] [Full Text] [PDF]

				C. J. Gallagher, K. L. Keene, J. C. Mychaleckyj, C. D. Langefeld, J. N. Hirschhorn, B. E. Henderson, C. J. Gordon, B. I. Freedman, S. S. Rich, D. W. Bowden, et al. Investigation of the Estrogen Receptor-{alpha} Gene With Type 2 Diabetes and/or Nephropathy in African-American and European-American Populations Diabetes, March 1, 2007; 56(3): 675 - 684. [Abstract] [Full Text] [PDF]

				J. A Riancho, M. T Zarrabeitia, C. Valero, C. Sanudo, V. Mijares, and J. Gonzalez-Macias A gene-to-gene interaction between aromatase and estrogen receptors influences bone mineral density. Eur. J. Endocrinol., July 1, 2006; 155(1): 53 - 59. [Abstract] [Full Text] [PDF]