Skip to main content
Log in

Bone mineral density, carotid artery intima-media thickness, and Klotho gene polymorphism in postmenopausal women

  • Research Article
  • Published:
Central European Journal of Medicine

Abstract

Aims

To evaluate the relationships between F352V polymorphism of Klotho gene, bone mineral density (BMD), and intima-media thickness (IMT) of the common carotid artery in postmenopausal women.

Methods

Spine and hip BMD was assessed by dual energy X-ray absorptiometry (DXA), and IMT was measured by ultrasonography in 184 postmenopausal women. The genotyping of the Klotho gene was performed by polymerase chain reaction-restriction fragment length polymorphism.

Results

Genotype frequencies were 81.5% for the homozygous wild type FF and 18.5% for the combined FV and VV genotypes. There were no significant differences in BMD at any site of measurement and mean carotid artery IMT across Klotho genotypes. In regression analysis, femoral neck BMD, but not total hip or lumbar spine BMD, was negatively associated with mean carotid IMT (p = 0.04). Patients with low femoral neck BMD had a significantly higher prevalence of carotid artery plaques as compared to those with normal BMD (p = 0.01).

Conclusion

The F352V polymorphism in the Klotho gene does not have a significant influence on bone mass and carotid atherosclerosis in postmenopausal women. Femoral neck BMD is associated with mean carotid IMT, suggesting that low bone mass may identify postmenopausal women at risk of atherosclerotic CVD.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CVD:

Cardiovascular diseases

BMD:

Bone mineral density

IMT:

Intima-media thickness

DXA:

Dual Energy X-ray Absorptiometry

SNPs:

Single nucleotide polymorphisms

BMI:

Body mass index

References

  1. Farhat G.N., Cauley J.A., The link between osteoporosis and cardiovascular disease, Clin. Cases Miner. Bone. Metab., 2008, 5, 19–34

    PubMed Central  PubMed  Google Scholar 

  2. Qu X., Huang X., Jin F., Wang H., Yongqiang H., Tanq T., et al., Bone mineral density and all-cause, cardiovascular and stroke mortality: A meta-analysis of prospective cohort studies, Int. J. Cardiol., 2013, 166, 385–393

    Article  PubMed  Google Scholar 

  3. den Uyl D., Nurmohamed M.T., van Tuyl L.H., Raterman H.G., Lems W.F., (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis, Arthritis Res. Ther., 2011, 13, R5

    Article  Google Scholar 

  4. Sennerby U., Melhus H., Gedeborg R., Byberg L., Garmo H., Ahlbom A., et al., Cardiovascular diseases and risk of hip fracture., JAMA., 2009, 302, 1666–1673

    Article  CAS  PubMed  Google Scholar 

  5. Bucay N., Sarosi I., Dunstan C.R., Morony S., Tarpley J., Capparelli C., et al., Osteoprotegerindeficient mice develop early onset osteoporosis and arterial calcification, Genes Dev., 1998, 12, 1260–1268

    Article  CAS  PubMed  Google Scholar 

  6. Elosua R., Ordovas J.M., Cupples L.A., Fox C.S., Polak J.F., Wolf P.A., et al., Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study, J. Lipid. Res., 2004, 45, 1868–1875

    Article  CAS  PubMed  Google Scholar 

  7. Cauley J.A., Zmuda J.M., Yaffe K., Kuller L.H., Ferrell R.E., Wisniewski S.R., et al., Apolipoprotein E polymorphism: A new genetic marker of hip fracture risk—The Study of Osteoporotic Fractures, J. Bone Miner. Res., 1999, 14, 1175–1181

    Article  CAS  PubMed  Google Scholar 

  8. Luo G., Ducy P., McKee M.D., Pinero G.J., Loyer E., Behringer R.R., et al., Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein, Nature, 1997, 386, 78–81

    Article  CAS  PubMed  Google Scholar 

  9. Kuro-o M., Matsumura Y., Aizawa H., Kawaguchi H., Suga T., Utsugi T., et al., Mutation of the mouse Klotho gene leads to a syndrome resembling ageing, Nature, 1997, 390, 45–51

    Article  CAS  PubMed  Google Scholar 

  10. Arking D.E., Krebsova A., Macek M. Sr., Macek M. Jr., Arking A., Mian I.S., et al., Association of human aging with a functional variant of Klotho, Proc. Natl. Acad. Sci. USA., 2002, 99, 856–861

    Article  CAS  PubMed  Google Scholar 

  11. Arking D.E., Atzmon G., Arking A., Barzilai N., Dietz H.C., Association between the functional variant of Klotho allele and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity, Circ. Res., 2005, 96, 412–418

    Article  CAS  PubMed  Google Scholar 

  12. Arking D.E., Becker D.M., Yanek L.R., Fallin D., Judge D.P., Moy T.F., et al., Klotho allele status and the risk of early-onset occult coronary artery disease., Am. J. Hum. Genet., 2003, 72, 1154–1161

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Majumdar V., Dindagur Nagaraja D., Christopher R., Association of the functional KL-VS variant of Klotho gene with early-onset ischemic stroke, Biochem. Biophys. Res. Commun., 2010, 403, 412–416

    Article  CAS  PubMed  Google Scholar 

  14. Nzietchueng R., El Shamieh S., Benachour H., Labat C., Herbeth B., Ndiaye N.C., et al., Klotho KL-VS genotype is involved in blood pressure regulation, Clin. Chim. Acta., 2011, 412, 1773–1777

    Article  CAS  PubMed  Google Scholar 

  15. Majumdar V., Christopher R., Association of exonic variants of Klotho with metabolic syndrome in Asian Indians, Clin. Chim. Acta., 2011, 412, 1116–1121

    Article  CAS  PubMed  Google Scholar 

  16. Zarrabeitia M.T., Hernandez J.L., Valero C., Zarrabeitia A.L., Ortiz F., Gonzales-Marcias J., Riancho J.A., Klotho gene polymorphism and male bone mass, Calcif. Tissue Int., 2007, 80, 10–14

    Article  CAS  PubMed  Google Scholar 

  17. Lorenz M.W., Markus H.S., Bots M.L., Rosvall M., Sitzer M., Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis, Circulation, 2007, 115, 459–467

    Article  PubMed  Google Scholar 

  18. Jorgensen L., Joakimsen O., Rosvold Berntsen G.K., Heuch I., Jacobsen B.K., Low bone mineral density is related to echogenic carotid artery plaques: a population-based study, Am. J. Epidemiol., 2004, 160, 549–556

    Article  PubMed  Google Scholar 

  19. Kim S.H., Kim Y.M., Cho M.A., Rhee Y., Hur K.Y., Kang E.S., et al., Echogenic carotid artery plaques are associated with vertebral fractures in postmenopausal women with low bone mass, Calcif. Tissue. Int., 2008, 82, 411–417

    Article  CAS  PubMed  Google Scholar 

  20. Montalcini T., Emanuele V., Ceravolo R., Gorgone G., Sesti G., Perticone F., et al., Relation of low bone mineral density and carotid atherosclerosis in postmenopausal women, Am. J. Cardiol., 2004, 94, 266–269

    Article  PubMed  Google Scholar 

  21. Sumino H., Ichikawa S., Kasama S., Takahashi T., Sakamoto H., Kumakura H., et al., Relationship between carotid atherosclerosis and lumbar spine bone mineral density in postmenopausal women, Hypertens. Res., 2008, 31, 1191–1197

    Article  PubMed  Google Scholar 

  22. Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J. Hypertens. 2003, 21, 1011–1053

    Article  Google Scholar 

  23. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 1997, 20, 1183–1197

    Google Scholar 

  24. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al., European Association for Cardiovascular Prevention & Rehabilitation, ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur. Heart. J., 2011, 32, 1769–1818

    Article  PubMed  Google Scholar 

  25. Stein J.H., Korcarz C.E., Hurst R.T., Lonn E., Kendall C.B., Mohler E.R., et al., American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine, J. Am. Soc. Echocardiogr., 2008, 21, 93–111

    Article  PubMed  Google Scholar 

  26. Wolf I., Laitman Y., Rubinek T., Abramovitz L., Novikov I., Beeri R., et al., Functional variant of Klotho: a breast cancer risk modifier among BRCA1 mutation carriers of Ashkenazi origin, Oncogene, 2010, 29, 26–33

    Article  CAS  PubMed  Google Scholar 

  27. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis, WHO Technical Report Series 843, Geneva, WHO, 1994

    Google Scholar 

  28. Invidia L., Salvioli S., Altilia S., Pierini M., Panourgia M., Monti D., et al., The frequency of Klotho KLVS polymorphism in a large Italian population, from young subjects to centenarians, suggests the presence of specific time windows for its effect, Biogerontol., 2010, 11, 67–73

    Article  Google Scholar 

  29. Riancho J.A., Valero C., Hernandez J.L., Ortiz F., Zarrabeitia A., Alonso M.A., et al., Association of the F352V variant of the Klotho gene with bone mineral density, Biogerontology, 2007, 8, 121–127

    Article  CAS  PubMed  Google Scholar 

  30. Kawano K., Ogata N., Chiano M., Molloy H., Kleyn P., Spector T.D., et al., Klotho gene polymorphisms associated with bone density of aged postmenopausal women, J. Bone Miner. Res., 2002, 17, 1744–1751

    Article  CAS  PubMed  Google Scholar 

  31. Ogata N., Matsumura Y., Shiraki M., Kawano K., Koshizuka Y., Hosoi T., et al., Association of Klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women, Bone, 2002, 31, 37–42

    Article  CAS  PubMed  Google Scholar 

  32. Yamada Y., Ando F., Niino N., Shimokata H., Association of polymorphsms of the androgen receptor and Klotho genes with bone mineral density in Japanese women, J. Mol. Med. (Berl.)., 2005, 83, 50–57

    Article  CAS  PubMed  Google Scholar 

  33. Mullin B.H., Wilson S.G., Islam F.M., Calautti M., Dick I.M., Devine A., et al., Klotho gene polymorphisms are associated with osteocalcin levels but not bone density of aged postmenopausal women. Calcif. Tissue Int., 2005, 77, 145–151

    Article  CAS  PubMed  Google Scholar 

  34. Gueguen R., Jouanny P., Guillemin F., Kuntz C., Pourel, Siest G., Segregation analysis and variance components analysis of bonemineral density in healthy families, J. Bone Miner. Res., 1995, 10, 2017–2022

    Article  CAS  PubMed  Google Scholar 

  35. Stewart Y.L., Ralston S.H., Role of genetic factors in the pathogenesis of osteoporosis, J. Endocrinol., 2000, 166, 235–245

    Article  CAS  PubMed  Google Scholar 

  36. Ralston S.H., Genetics of osteoporosis, Proc. Nutr. Soc., 2007, 66, 158–165

    Article  CAS  PubMed  Google Scholar 

  37. Ralston S.H., Uitterlinden A.G., Genetics of osteoporosis, Endocr. Rev., 2010, 31, 629–662

    Article  CAS  PubMed  Google Scholar 

  38. Voght M.T., San Valentin R., Forrest K.Y., Nevitt M.C., Cauley J.A., Bone Mineral density and aortic calcification: the Study of Osteoporotic Fractures, J. Am. Geriatr. Soc., 1997, 45, 140–145

    Google Scholar 

  39. Aoyagi K., Ross P.D., Orloff J., Davis K.W., Katagiri H., Washnich R.D., Low bone density is not associated with aortic calcification, Calcif. Tissue Int., 2001, 69, 20–24

    Article  CAS  PubMed  Google Scholar 

  40. McFarlane S.I., Muniyappa R., Shin J.J., Bahtiyar G., Sowers J.R., Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?, Endocrine, 2004, 23, 1–10

    Article  CAS  PubMed  Google Scholar 

  41. Anagnostis A., Karagiannis A., Kakafika A.I., Tziomalos K., Athyros V.G., Mikhailidis D.P., Atherosclerosis and osteoporosis: age-dependent degenerative processes or related entities?, Osteoporos. Int., 2009, 20, 197–207

    Article  CAS  PubMed  Google Scholar 

  42. Banks L.M., Lees B., Macsweeney J.E., Stevenson J.C., Effect of degenerative spinal and aortic calcification on bone density measurements in postmenopausal women: links between osteoporosis and cardiovascular disease?, Eur. J. Clin. Invest., 1994, 24, 813–817

    Article  CAS  PubMed  Google Scholar 

  43. Uyama O., Yoshimoto Y., Yamamoto Y., Kawai A., Bone changes and carotid atherosclerosis in postmenopausal women, Stroke, 1997, 8, 1730–1732

    Article  Google Scholar 

  44. Hmamouchi I., Allali F., Khazzani H., Bennani L., El Mansouri L., Ichchou L., et al., Low bone mineral density is realated to atherosclerosis in postmenopausal Marocan women, BMC Public Health, 2009, 9, 388

    Article  PubMed Central  PubMed  Google Scholar 

  45. Shaffer J.R., Kammerer C.M., Rainwater D.L., O’Leary D.H., Bruder J.M., Bauer R.L., et al., Decreased bone mineral density is correlated with increased subclinical atherosclerosis in older, but not younger, Mexican American women and men: the San Antonio Family Osteoporosis Study, Calcif. Tissue Int., 2007, 81, 430–441

    Article  CAS  PubMed  Google Scholar 

  46. Frye M.A., Melton L.J. 3rd, Bryant S.C., Fitzpatrick L.A., Wahner H.W., Scwartz R.S., et al., Osteoporosis and calcification of the aorta, Bone Miner., 1992, 19, 185–194

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniela Fodor.

About this article

Cite this article

Muntean, L., Simon, Sp., Popp, R. et al. Bone mineral density, carotid artery intima-media thickness, and Klotho gene polymorphism in postmenopausal women. cent.eur.j.med 9, 315–324 (2014). https://doi.org/10.2478/s11536-013-0273-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11536-013-0273-3

Keywords

Navigation