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.
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
Farhat G.N., Cauley J.A., The link between osteoporosis and cardiovascular disease, Clin. Cases Miner. Bone. Metab., 2008, 5, 19–34
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
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
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
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
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
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
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
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
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
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
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
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
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
Majumdar V., Christopher R., Association of exonic variants of Klotho with metabolic syndrome in Asian Indians, Clin. Chim. Acta., 2011, 412, 1116–1121
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
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
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
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
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
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
Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J. Hypertens. 2003, 21, 1011–1053
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
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
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
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
World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis, WHO Technical Report Series 843, Geneva, WHO, 1994
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
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
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
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
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
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
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
Stewart Y.L., Ralston S.H., Role of genetic factors in the pathogenesis of osteoporosis, J. Endocrinol., 2000, 166, 235–245
Ralston S.H., Genetics of osteoporosis, Proc. Nutr. Soc., 2007, 66, 158–165
Ralston S.H., Uitterlinden A.G., Genetics of osteoporosis, Endocr. Rev., 2010, 31, 629–662
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
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
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
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
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
Uyama O., Yoshimoto Y., Yamamoto Y., Kawai A., Bone changes and carotid atherosclerosis in postmenopausal women, Stroke, 1997, 8, 1730–1732
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
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
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
Author information
Authors and Affiliations
Corresponding author
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11536-013-0273-3