Skip to main content

Advertisement

SpringerLink
Log in

Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

We assessed the main and interaction effects of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. A total of 228 premenarche Chinese girls (9–11.5 years old) were recruited for a 2-year follow-up study. Bone mineral density (BMD) at the total body, lumbar spine (L1–L4), and total left hip were measured by dual-energy X-ray absorptiometry at baseline and follow-up. The −174G/C and −634C/G polymorphism of IL-6 gene, and PvuII and XbaI polymorphisms of the estrogen receptor (ER)-α gene, were determined. The −634C/G polymorphism of the IL-6 gene and PvuII polymorphism of ER-α gene were significantly associated with bone mass accrual after adjusting the potential confounding factors. Girls with pp genotype of ER-α gene had greater percentage accrual in BMD of total body (P = 0.010) and femoral intertrochanter (P = 0.038) than their PP and Pp counterparts. Girls with CC genotype of IL-6 −634G/C gene had higher percentage accrual in BMD of total body (P = 0.032) and femoral trochanter (P = 0.048) than their CG + GG counterparts. Significant interaction effects of IL-6 −634C/G polymorphism and ER-α PvuII polymorphism were observed on percentage change in BMD of total left hip (P = 0.009) and femoral intertrochanter (P = 0.007). The genotype CC (IL-6 −634C/G) × pp (ER-α PvuII) was associated with greater BMD accrual than other genotype combination in Chinese adolescent girls. We found that the IL-6 −634C/G and ER-α PvuII polymorphism were significantly associated with BMD accrual and that they have an interactional effect on BMD accrual in Chinese adolescent girls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kelly PJ, Morrison NA, Sambrook PN, Nguyen TV, Eisman JA (1995) Genetic influences on bone turnover, bone density and fracture. Eur J Endocrinol 133:265–271

    Article  PubMed  CAS  Google Scholar 

  2. Liu YZ, Liu YJ, Recker RR, Deng HW (2003) Molecular studies of identification of genes for osteoporosis: the 2002 update. J Endocrinol 177:147–196

    Article  PubMed  CAS  Google Scholar 

  3. Ho NC, Jia L, Driscoll CC, Gutter EM, Francomano CA (2000) A skeletal gene database. J Bone Miner Res 15:2095–2122

    Article  PubMed  CAS  Google Scholar 

  4. Manolagas SC, Jilka RL (1995) Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332:305–311

    Article  PubMed  CAS  Google Scholar 

  5. Manolagas SC (1998) The role of IL-6 type cytokines and their receptors in bone. Ann NY Acad Sci 840:194–204

    Article  PubMed  CAS  Google Scholar 

  6. Garnero P, Borel O, Sornay-Rendu E, Duboeuf F, Jeffery R, Woo P, Delmas PD (2002) Association between a functional interleukin-6 gene polymorphism and peak bone mineral density and postmenopausal bone loss in women: The OFELY study. Bone 31:43–50.

    Article  PubMed  CAS  Google Scholar 

  7. Ota N, Nakajima T, Nakazawa I, Suzuki T, Hosoi T, Orimo H, Inoue S, Shirai Y, Emi M (2001) A Nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density. J Hum Genet 46:267–272

    Article  PubMed  CAS  Google Scholar 

  8. Spelsberg TC, Subramaniam M, Riggs BL, Khosla S (1999) The actions and interactions of sex steroids and growth factors/cytokines on the skeleton. Mol Endocrinol 13:819–828

    Article  PubMed  CAS  Google Scholar 

  9. Mitra S, Desai M, Khatkhatay MI (2006) Association of estrogen receptor alpha gene polymorphisms with bone mineral density in postmenopausal Indian women. Mol Genet Metab 87(1):80–87

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Gennari L, Becherini L, Masi L, Mansani R, Gonnelli S, Cepollaro C, Martini S, Montagnani A, Lentini G, Becorpi AM, Brandi ML (1998) Vitamin D and estrogen receptor allelic variants in Italian postmenopausal women: evidence of multiple gene contribution to bone mineral density. J Clin Endocrinol Metab 83:939–944

    Article  PubMed  CAS  Google Scholar 

  12. Rifas L, Kenney JS, Marcelli M, Pacifici R, Cheng SL, Dawson LL, Avioli LV (1995) Production of interleukin-6 in human osteoblasts and human bone marrows tromal cells: evidence that induction by interleukin-1 and tumor necrosis factor-alpha is not regulated by ovarian steroids. Endocrinology 136(9):4056–4067

    Article  PubMed  CAS  Google Scholar 

  13. Willing M, Sowers M, Aron D, Clark MK, Burns T, Bunten C, Crutchfield M, D’Agostino D, Jannausch M (1998) Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction. J Bone Miner Res 13(4):695–705

    Article  PubMed  CAS  Google Scholar 

  14. Nasu M, Sugimoto T, Kaji H, Chihara K (2000) Estrogen modulates osteoblast proliferation and function regulated by parathyroid hormone in osteoblastic SaOS-2 cells: role of insulin-like growth factor (IGF)-I and IGF-binding protein-5. J Endocrinol 167(2):305–313

    Article  PubMed  CAS  Google Scholar 

  15. Uitterlinden AG, Weel AE, Burger H, Fang Y, van Duijn CM, Hofman A, van Leeuwen JP, Pols HA (2001) Interaction between the vitamin D receptor gene and collagen type alpha gene in susceptibility for fracture. J Bone Miner Res 16(2):379–385

    Article  PubMed  CAS  Google Scholar 

  16. Garcia-Giralt N, Nogues X, Enjuanes A, Puig J, Mellibovsky L, Bay-Jensen A, Carreras R, Balcells S, Diez-Perez A, Grinberg D (2000) Two new single-nucleotide polymorphisms in the COL1A1 upstream regulatory region and their relationship to bone mineral density. J Bone Miner Res 17(3):384–393

    Article  Google Scholar 

  17. Crocker PRE, Bailey DA, Faulkner RA, Kowalski KC, McGrath R (1997) Measuring general levels of physical activity: preliminary evidence for the Physical Activity Questionnaire for Children. Med Sci Sports Exerc 29(10):1344–1349

    PubMed  CAS  Google Scholar 

  18. Ferrari SL, Garnero P, Emond S, Montgomery H, Humphries SE, Greenspan SL (2001) A functional polymorphic variant in the interlrukin-6 gene promoter associated with low bone resorption in postmenopausal women. Arthritis Rheum 44:196–201

    Article  PubMed  CAS  Google Scholar 

  19. Lei SF, Liu YZ, Deng FY, Li YM, Li MX, Deng HW (2005) Association and linkage analyses of interleukin-6 gene 634C/G polymorphism and bone phenotypes in Chinese. J Bone Miner Metab 23(4):323–328

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  21. Cohen J (1988) The analysis of variance and covariance. In: Statistical Power Analysis for the Behavioural Sciences, 2nd edn. Erlbaum Associates, Hillsdale, NJ, pp 273–406

    Google Scholar 

  22. Rubin LA, Hawker GA, Peltekova VD, Fielding LJ, Ridout R, Cole DE (1999) Determinants of peak bone mass: clinical and genetic analyses in a young female Canadian cohort. J Bone Miner Res 14:633–643

    Article  PubMed  CAS  Google Scholar 

  23. Hayakawa T, Takamura T, Hisada A, Abe T, Nomura G, Kobayashi K (2001) IL-6 gene polymorphism −174G/C does not contribute substantially to hyperlipidaemia and type II diabetes mellitus in Japanese men. Diabetologia 45:453–454

    Google Scholar 

  24. Zhai R, Liu G, Yang C, Huang C, Wu C, Christiani DC (2001) The G to C polymorphism at −174 of the interleukin-6 gene is rare in the Southern Chinese population. Pharmacogenetics 11:699–701

    Article  PubMed  CAS  Google Scholar 

  25. Lei SF, Deng FY, Liu XH, Huang QR, Qin YJ, Zhou Q, Jiang DK, Li YM, Mo XY, Liu MY, Chen XD, Wu XS, Shen H, Dvornyk V, Zhao LJ, Recker RR, Deng HW (2003) Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity. J Bone Miner Metab 21:34–42

    Article  PubMed  CAS  Google Scholar 

  26. Yamada Y, Ando F, Niino N, Shimokata H (2003) Association of polymorphisms of interleukin-6, osteocalcin, and vitamin D receptor genes, alone or in combination, with bone mineral density in community-dwelling Japanese women and men. J Clin Endocrinol Metab 88(7):3372–3378

    Article  PubMed  CAS  Google Scholar 

  27. Ota N, Nakajima T, Nakazawa I, Suzuki T, Hosoi T, Orimo H, Inoue S, Shirai Y, Emi M (2001) A nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density. J Hum Genet 46:267–272

    Article  PubMed  CAS  Google Scholar 

  28. Huang Q, Wang Q, Zhang L, Liu J, Zhou Q, Liu Y, He J, Lin F (1999) Relationship between bone mineral density and polymorphism of the estrogen receptor gene in healthy postmenopausal women in China. Chin Med J (Engl) 112(9):832–835

    CAS  Google Scholar 

  29. Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Saarikoski S, Honkanen R, Maenpaa PH (2000) Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: effect of hormone replacement therapy. J Bone Miner Res 15:315–321

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  31. Dennison E, Syddall H, Fall C, Brandi ML, Cooper C, Hertfordshire Cohort Study Group (2005) Evidence of sexual dimorphism in relationships between estrogen receptor polymorphisms and bone mass: the Hertfordshire study. J Rheumatol 32(12):2400–2404.

    PubMed  CAS  Google Scholar 

  32. Jian WX, Yang YJ, Long JR, Li YN, Deng FY, Jiang DK, Deng HW (2005) Estrogen receptor alpha gene relationship with peak bone mass and body mass index in Chinese nuclear families. J Hum Genet 50(9):477–482

    Article  PubMed  CAS  Google Scholar 

  33. Nishimura R, Moriyama K, Yasukawa K, Mundy GR, Yoneda T (1998) Combination of interleukin-6 and soluble interleukin-6 receptors induces differentiation and activation of JAK-STAT and MAP kinase pathways in MG-63 human osteoblastic cells. J Bone Miner Res 13(5):777–785

    Article  PubMed  CAS  Google Scholar 

  34. Pacifici R (1996) Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11(8):1043–1051

    Article  PubMed  CAS  Google Scholar 

  35. Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Willams DC, Manolagas SC (1996) 17-Beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89(3):883–891

    Article  Google Scholar 

  36. Abrahamsen B, Bonnevie-Nielsen V, Ebbesen EN, Gram J, Beck-Nielsen H (2000) Cytokines and bone loss in a 5-year longitudinal study: hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study. J Bone Miner Res 15(8):1545–1554

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhongshan Rd 2, Guangzhou, 510080, China

    Li Xing, Guo-peng He, Yu-ming Chen & Yi-xiang Su

  2. The Institute of Health Inspection, Guangzhou, China

    Li Xing

Authors
  1. Li Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guo-peng He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu-ming Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi-xiang Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi-xiang Su.

About this article

Cite this article

Xing, L., He, Gp., Chen, Ym. et al. Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. J Bone Miner Metab 26, 493–498 (2008). https://doi.org/10.1007/s00774-007-0844-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-007-0844-y

Key words

Search

Navigation