Skip to main content
SpringerLink
Log in

The association between genetic variants of RUNX2, ADIPOQ and vertebral fracture in Korean postmenopausal women

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

Abstract

Contrary to the traditional belief that obesity acts as a protective factor for bone, recent epidemiologic studies have shown that body fat might be a risk factor for osteoporosis and bone fracture. Accordingly, we evaluated the association between the phenotypes of osteoporosis or vertebral fracture and variants of obesity-related genes, peroxisome proliferator-activated receptor-gamma (PPARG), runt-related transcription factor 2 (RUNX2), leptin receptor (LEPR), and adiponectin (ADIPOQ). In total, 907 postmenopausal healthy women, aged 60–79 years, were included in this study. BMD and biomarkers of bone health and adiposity were measured. We genotyped for four single nucleotide polymorphisms (SNPs) from four genes (PPARG, RUNX2, LEPR, ADIPOQ). A general linear model for continuous dependent variables and a logistic regression model for categorical dependent variables were used to analyze the statistical differences among genotype groups. Compared with the TT subjects at rs7771980 in RUNX2, C-carrier (TC + CC) subjects had a lower vertebral fracture risk after adjusting for age, smoking, alcohol, total calorie intake, total energy expenditure, total calcium intake, total fat intake, weight, body fat. Odds ratio (OR) and 95 % interval (CI) for the vertebral fracture risk was 0.55 (95 % CI 0.32–0.94). After adjusting for multiple variables, the prevalence of vertebral fracture was highest in GG subjects at rs1501299 in ADIPOQ (p = 0.0473). A high calcium intake (>1000 mg/day) contributed to a high bone mineral density (BMD) in GT + TT subjects at rs1501299 in ADIPOQ (p for interaction = 0.0295). Even if the mechanisms between obesity-related genes and bone health are not fully established, the results of our study revealed the association of certain SNPs from obesity-related genes with BMD or vertebral fracture risk in postmenopausal Korean women.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Guney E, Kisakol G, Ozgen G, Yilmaz C, Yilmaz R, Kabalak T (2003) Effect of weight loss on bone metabolism: comparison of vertical banded gastroplasty and medical intervention. Obes Surg 13:383–388

    Article  PubMed  Google Scholar 

  2. Radak TL (2004) Caloric restriction and calcium’s effect on bone metabolism and body composition in overweight and obese premenopausal women. Nutr Rev 62:468–481

    Article  PubMed  Google Scholar 

  3. Wardlaw GM (1996) Putting body weight and osteoporosis into perspective. Am J Clin Nutr 63:433S–436S

    CAS  PubMed  Google Scholar 

  4. Hsu YH, Venners SA, Terwedow HA, Feng Y, Niu T, Li Z (2006) Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women. Am J Clin Nutr 83:146–154

    CAS  PubMed  Google Scholar 

  5. Janicka A, Wren TA, Sanchez MM, Dorey F, Kim PS, Mittelman SD (2007) Fat mass is not beneficial to bone in adolescents and young adults. J Clin Endocrinol Metab 92:143–147

    Article  CAS  PubMed  Google Scholar 

  6. Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW (2007) Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 92:1640–1646

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B (2004) Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 3:379–389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA (2004) Adiponectin and its receptors are expressed in bone-forming cells. Bone 35:842–849

    Article  CAS  PubMed  Google Scholar 

  9. Cornish J, Callon KE, Bava U, Lin C, Naot D, Hill BL (2002) Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol 175:405–415

    Article  CAS  PubMed  Google Scholar 

  10. Luo XH, Guo LJ, Xie H, Yuan LQ, Wu XP, Zhou HD (2006) Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res 21:1648–1656

    Article  CAS  PubMed  Google Scholar 

  11. Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG (2000) Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 92:73–78

    Article  CAS  PubMed  Google Scholar 

  12. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) (2001) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 285:2486–2497

    Google Scholar 

  13. Ferrar L, Jiang G, Adams J, Eastell R (2005) Identification of vertebral fractures: an update. Osteoporos Int 16:717–728

    Article  CAS  PubMed  Google Scholar 

  14. Ribas-Barba L, Serra-Majem L, Roman-Vinas B, Ngo J, Garcia-Alvarez A (2009) Effects of dietary assessment methods on assessing risk of nutrient intake adequacy at the population level: from theory to practice. Br J Nutr 101:S64–S72

    Article  CAS  PubMed  Google Scholar 

  15. Bustamante M, Nogues X, Agueda L, Jurado S, Wesselius A, Caceres E (2007) Promoter 2–1025 T/C polymorphism in the RUNX2 gene is associated with femoral neck bmd in Spanish postmenopausal women. Calcif Tissue Int 81:327–332

    Article  CAS  PubMed  Google Scholar 

  16. Doecke JD, Day CJ, Stephens AS, Carter SL, van Daal A, Kotowicz MA (2006) Association of functionally different RUNX2 P2 promoter alleles with BMD. J Bone Miner Res 21:265–273

    Article  CAS  PubMed  Google Scholar 

  17. Rhee EJ, Oh KW, Lee WY, Kim SY, Oh ES, Baek KH (2006) Effects of two common polymorphisms of peroxisome proliferator-activated receptor-gamma gene on metabolic syndrome. Arch Med Res 7:86–94

    Article  Google Scholar 

  18. Kiel D, Ferrari S, Cupples L (2005) Polymorphisms in the PPARγ gene influence bone density in humans. J Bone Miner Res 20:S234

    Google Scholar 

  19. Lee WY, Rhee EJ, Oh KW, Kim SY, Jung CH, Yun EJ (2006) Identification of adiponectin and its receptors in human osteoblast-like cells and association of T45G polymorphism in exon 2 of adiponectin gene with lumbar spine bone mineral density in Korean women. Clin Endocrinol (Oxf). 65:631–637

    Article  CAS  PubMed  Google Scholar 

  20. Zhang ZL, He JW, Qin YJ, Hu YQ, Li M, Liu YJ (2007) Association between SNP and haplotypes in PPARGC1 and adiponectin genes and bone mineral density in Chinese nuclear families. Acta Pharmacol Sin 28:287–295

    Article  CAS  PubMed  Google Scholar 

  21. Crabbe P, Goemaere S, Zmierczak H, Van Pottelbergh I, De Bacquer D, Kaufman JM (2006) Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men? Eur J Endocrinol 154:707–714

    Article  CAS  PubMed  Google Scholar 

  22. Fairbrother UL, Tanko LB, Walley AJ, Christiansen C, Froguel P, Blakemore AI (2007) Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women. J Bone Miner Res 22:544–550

    Article  CAS  PubMed  Google Scholar 

  23. Koh JM, Kim DJ, Hong JS, Park JY, Lee KU, Kim SY (2002) Estrogen receptor alpha gene polymorphisms Pvu II and Xba I influence association between leptin receptor gene polymorphism (Gln223Arg) and bone mineral density in young men. Eur J Endocrinol 147:777–783

    Article  CAS  PubMed  Google Scholar 

  24. Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B (2008) Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 93:1217–1223

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Iwamoto J, Takeda T, Sato Y (2006) Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Curr Drug Saf 1:87–97

    Article  CAS  PubMed  Google Scholar 

  26. Li R, Svenson KL, Donahue LR, Peters LL, Churchill GA (2008) Relationships of dietary fat, body composition, and bone mineral density in inbred mouse strain panels. Physiol Genomics 33:26–32

    Article  PubMed  Google Scholar 

  27. Reid IR, Ames R, Mason B, Reid HE, Bacon CJ, Bolland MJ (2008) Randomized controlled trial of calcium supplementation in healthy, nonosteoporotic, older men. Arch Intern Med 168:2276–2282

    Article  CAS  PubMed  Google Scholar 

  28. Song Y, Paik HY, Joung H (2008) Soybean and soy isoflavone intake indicate a positive change in bone mineral density for 2 years in young Korean women. Nutr Res 28:25–30

    Article  CAS  PubMed  Google Scholar 

  29. Ward WE, Fonseca D (2007) Soy isoflavones and fatty acids: effects on bone tissue postovariectomy in mice. Mol Nutr Food Res 51:824–831

    Article  CAS  PubMed  Google Scholar 

  30. Yazdanpanah N, Zillikens MC, Rivadeneira F, de Jong R, Lindemans J, Uitterlinden AG (2007) Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study. Bone 41:987–994

    Article  CAS  PubMed  Google Scholar 

  31. Zhu K, Bruce D, Austin N, Devine A, Ebeling PR, Prince RL (2008) Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J Bone Miner Res 23:1343–1348

    Article  CAS  PubMed  Google Scholar 

  32. Zhu K, Devine A, Dick IM, Wilson SG, Prince RL (2008) Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. J Clin Endocrinol Metab 93:743–749

    Article  CAS  PubMed  Google Scholar 

  33. Sun X, Zemel MB (2007) Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity (Silver Spring) 15:340–348

    Article  CAS  Google Scholar 

Download references

Conflict of interest

All authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Family Medicine, Chaum Hospital, Cha University, Seoul, Korea

    Kyong-Chol Kim

  2. Health Promotion Center, Ewha Woman’s University Mokdong Hospital Ewha Woman’s University School of Medicine, Seoul, Korea

    Hyejin Chun

  3. Nutritional Genomics Lab, Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

    ChaoQiang Lai, Laurence D. Parnell & Jose. M. Ordovas

  4. Graduate Program in Science for Aging, Yonsei University, Seoul, Korea

    Yangsoo Jang & Jongho Lee

Authors
  1. Kyong-Chol Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyejin Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ChaoQiang Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laurence D. Parnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yangsoo Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jongho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jose. M. Ordovas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyong-Chol Kim.

About this article

Cite this article

Kim, KC., Chun, H., Lai, C. et al. The association between genetic variants of RUNX2, ADIPOQ and vertebral fracture in Korean postmenopausal women. J Bone Miner Metab 33, 173–179 (2015). https://doi.org/10.1007/s00774-014-0570-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-014-0570-1

Keywords

Search

Navigation