Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Association of polymorphisms in the estrogen receptor α gene with body fat distribution

Abstract

OBJECTIVE: To examine whether polymorphisms of the estrogen receptor (ER) α gene are associated with body fat distribution.

DESIGN: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T → C (PvuII) and an A → G (XbaI), in the first intron of the ERα gene.

SUBJECTS: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40–79 y).

MEASUREMENTS: The ERα genotypes (by automated fluorescent allele-specific DNA primer assay system), anthropometric variables, fat mass (FM) and percentage FM (%FM) (by dual-energy X-ray absorptiometry).

RESULTS: FM and waist were inversely associated with age (r=−0.630 and −0.504, respectively) in women with the GG genotype. On the other hand, waist circumference of the AA genotype was positively correlated with age (r=0.231). Thus, for middle-aged women (40–59 y) with the AG or GG genotype body mass index (BMI), %FM, FM, waist, hip and waist-to-hip ratio (WHR) were larger than those with the AA genotype. In particular, FM and waist were greater by 20% and 9%, respectively, for the GG genotype, compared to the AA genotype. Alternatively, FM and waist were smaller by 18% and 6%, respectively, in older women with the GG genotype, compared to the AA genotype. No effect was found among the A → G polymorphisms for men. For both genders, no difference was found in any variables among the TT, TC and CC genotypes with the exception of BMI of older men (60–79 y).

CONCLUSION: No association was found between the ERα gene polymorphisms and body fat distribution in men. For women, the A → G polymorphism, in particular the GG genotype, may contribute to the development of upper-body obesity in middle-aged individuals, but may serve to decrease the whole-body and abdominal fat tissue of older individuals.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kissebah AH, Peiris AN . Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus. Diabetes Metab Rev 1989; 5: 83–109.

    Article  CAS  PubMed  Google Scholar 

  2. Kissebah AH, Vydelungum N, Murray R . Relation of body distribution to metabolic complication of obesity. J Clin Endocrinol Metab 1982; 54: 163–170.

    Article  Google Scholar 

  3. Micciolo R, Bosello O, Ferrari P, Armellini F . The association of body fat location with hemodynamics and metabolic status in men and women aged 21–60. J Clin Epidemiol 1991; 6: 591–608.

    Article  Google Scholar 

  4. Vague J . The degree of masculine differentiation of obesities. Am J Clin Nutr 1956; 4: 20–34.

    Article  CAS  PubMed  Google Scholar 

  5. Gambacciani M, Ciaponi M, Cappagli B, Benussi C, De Simone L, Genazzani AR . Climacteric modifications in body weight and fat tissue distribution. Climacteric 1999; 2: 37–44.

    Article  CAS  PubMed  Google Scholar 

  6. Tchernof A, Poehlman ET, Despres JP . Body fat distribution, the menopause transition, and hormone replacement therapy. Diabetes Metab 2000; 26: 12–20.

    CAS  PubMed  Google Scholar 

  7. Davis SR, Walker KZ, Strauss BJ . Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Menopause 2000; 7: 395–401.

    Article  CAS  PubMed  Google Scholar 

  8. Perrone G, Liu Y, Capri O, Critelli C, Barillaro F, Galoppi P, Zichella L . Evaluation of the body composition and fat distribution in long-term users of hormone replacement therapy. Gynecol Obstet Invest 1999; 48: 52–55.

    Article  CAS  PubMed  Google Scholar 

  9. Tchernof A, Calles-Escandon J, Sites CK, Poehlman ET . Menopause, central body fatness, and insulin resistance: effects of hormone-replacement therapy. Coronary Artery Dis 1998; 9: 503–511.

    Article  CAS  Google Scholar 

  10. Perry AC, Allison M, Applegate EB, Jackson ML, Miller PC . The relationship between fat distribution and coronary risk factors in sedentary postmenopausal women on and off hormone replacement therapy. Obes Res 1998; 6: 40–46.

    Article  CAS  PubMed  Google Scholar 

  11. Albagha OM, McGuigan FE, Reid DM, Ralston SH . Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom. J Bone Miner Res 2001; 16: 128–134.

    Article  CAS  PubMed  Google Scholar 

  12. Becherini L, Gennari L, Masi L, Mansani R, Massart F, Morelli A, Falchetti A, Gonnelli S, Fiorelli G, Tanini A, Brandi ML . Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women. Hum Mol Genet 2000; 9: 2043–2050.

    Article  CAS  PubMed  Google Scholar 

  13. Ongphiphadhanakul B, Chanprasertyothin S, Payatikul P, Tung SS, Piaseu N, Chailurkit L, Chansirikarn S, Puavilai G, Rajatanavin R . Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women. Clin Endocrinol 2000; 52: 581–585.

    Article  CAS  Google Scholar 

  14. Ogawa S, Hosoi T, Shiraki M, Orimo H, Emi M, Muramatsu M, Ouchi Y, Inoue S . Association of estrogen receptor beta gene polymorphism with bone mineral density. Biochem Biophys Res Commun 2000; 269: 537–541.

    Article  CAS  PubMed  Google Scholar 

  15. Lorentzon M, Lorentzon R, Backstrom T, Nordstrom P . Estrogen receptor gene polymorphism, but not estradiol levels, is related to bone density in healthy adolescent boys: a cross-sectional and longitudinal study. J Clin Endocrinol Metab 1999; 84: 4597–4601.

    CAS  PubMed  Google Scholar 

  16. Deng HW, Li J, Li JL, Johnson M, Gong G, Davis KM, Recker RR . Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes. Hum Genet 1998; 103: 576–585.

    Article  CAS  PubMed  Google Scholar 

  17. Kobayashi S, Inoue S, Hosoi T, Ouchi Y, Shiraki M, Orimo H . Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res 1996; 11: 306–311.

    Article  CAS  PubMed  Google Scholar 

  18. Sano M, Inoue S, Hosoi T, Ouchi Y, Emi M, Shiraki M, Orimo H . Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis. Biochem Biophys Res Commun 1995; 217: 378–383.

    Article  CAS  PubMed  Google Scholar 

  19. Speer G, Cseh K, Winkler G, Vargha P, Braun E, Takacs I, Lakatos P . Vitamin D and estrogen receptor gene polymorphisms in type 2 diabetes mellitus and in android type obesity. Eur J Endocrinol 2001; 144: 385–389.

    Article  CAS  PubMed  Google Scholar 

  20. Niino M, Kikuchi S, Fukazawa T, Yabe I, Tashiro K . Estrogen receptor gene polymorphism in Japanese patients with multiple sclerosis. J Neurol Sci 2000; 179: 70–75.

    Article  CAS  PubMed  Google Scholar 

  21. Ponglikitmongkol M, Green S, Chambon P . Genomic organization of the human oestrogen receptor gene. EMBO J 1988; 7: 3385–3388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Willing M, Sowers M, Aron D, Clark MK, Burns T, Bunten C, Crutchfield M, D'Agostino D, Jannausch M . Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction. J Bone Miner Res 1998; 13: 695–705.

    Article  CAS  PubMed  Google Scholar 

  23. Patel MS, Cole DEC, Smith JD, Hawker GA, Wong B, Trang H, Vieth R, Meltzer P, Rubin LA . Alleles of the estrogen receptor α-gene and an estrogen receptor cotranscriptional activator gene, amplified in breast cancer-1 (AIBI1), are associated with quantitative calcaneal ultrasound. J Bone Miner Res 2000; 15: 2231–2239.

    Article  CAS  PubMed  Google Scholar 

  24. Salmén T, Heikkinen A-M, Mahonen A, Kröger H, Komulainen M, Saarikoski S, Honkanen R, Mäenpää P . The protective effect of hormone-replacement therapy on fracture risk is modulated by estrogen receptor α genotype in early postmenopausal women. J Bone Miner Res 2000; 15: 2479–2486.

    Article  PubMed  Google Scholar 

  25. Shimokata H, Ando F, Niino N . A new comprehensive study on aging — the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). J Epidemiol 2000; 10: S1–S9.

    Article  CAS  PubMed  Google Scholar 

  26. Yamada Y, Ando F, Niino N, Shimokata H . Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density in community-dwelling Japanese. Int J Mol Med 2002; 80: 452–460.

    Article  CAS  Google Scholar 

  27. Taylor HL, Jacobs Jr DR, Shucker B, Knudsen J, Leon AS, DeBacker G . A questionnaire for the assessment of leisure-time physical activities. J Chron Dis 1978; 31: 741–755.

    Article  CAS  PubMed  Google Scholar 

  28. Montoye HJ . Estimation of habitual physical activity by questionnaire and interview. Am J Clin Nutr 1971; 24: 1113–1118.

    Article  CAS  PubMed  Google Scholar 

  29. Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    Article  CAS  PubMed  Google Scholar 

  30. Thompson EA, Deeb S, Walker D, Motulsky AG . The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet 1988; 42: 113–124.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Rankinen T, Perusse L, Weisnagel SJ, Snyder EE, Chagnon YC, Bouchard C . The human obesity gene map: the 2001 update. Obes Res 2002; 10: 196–243.

    Article  CAS  PubMed  Google Scholar 

  32. Macor C, Ruggeri A, Mazzonetto P, Federspil G, Cobelli C, Vettor R . Visceral adipose tissue impairs insulin secretion and insulin sensitivity but not energy expenditure in obesity. Metabolism 1997; 46: 123–129.

    Article  CAS  PubMed  Google Scholar 

  33. Cooke PS, Heine PA, Taylor JA, Lubahn DB . The role of estrogen and estrogen receptor-alpha in male adipose tissue. Mol Cell Endocrinol 2001; 178: 147–154.

    Article  CAS  PubMed  Google Scholar 

  34. Snijder MB, Dekker JM, Visser M, Yudkin JS, Stehouwer CD, Bouter LM, Heine RJ, Nijpels G, Seidell JC . Larger thigh and hip circumferences are associated with better glucose tolerance: the horn study. Obes Res 2003; 11: 104–111.

    Article  PubMed  Google Scholar 

  35. Goessl C, Plaschke J, Pistorius S, Hahn M, Frank S, Hampl M, Gorgens H, Koch R, Saeger HD, Schackert HK . An intronic germline transition in the HNPCC gene hMSH2 is associated with sporadic colorectal cancer. Eur J Cancer 1997; 33: 1869–1874.

    Article  CAS  PubMed  Google Scholar 

  36. Blaszyk H, Hartmann A, Sommer SS, Kovach JS . A polymorphism but no mutations in the GADD45 gene in breast cancers. Hum Genet 1996; 97: 543–547.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to the participants in the study. We also thank all the investigators, research assistants and laboratory technicians who have contributed to this study. This study was supported by a Grant-in-Aid for comprehensive Research on Aging and Health from the Ministry of Health, Labour and Welfare of Japan.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T Okura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Okura, T., Koda, M., Ando, F. et al. Association of polymorphisms in the estrogen receptor α gene with body fat distribution. Int J Obes 27, 1020–1027 (2003). https://doi.org/10.1038/sj.ijo.0802378

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802378

Keywords

This article is cited by

Search

Quick links