Abstract
Osteoporosis is a disease with complex etiology where the genetic factors may account for as much as 50–85% of the risk of its development in postmenopausal women. The polymorphism of estrogen receptor genes (ESR1, ESR2) seems essential among the genetic factors. The goal of this study was to analyze polymorphisms of selected genes in a population of postmenopausal women treated for osteoporosis and to evaluate the influence of genetic and nongenetic factors on the estimated 10-year risk of fracture. The study group consisted of 214 women hospitalized for treatment of postmenopausal osteoporosis. We investigated the presence of ESR1, ESR2, LRP5, and WNT16 genetic polymorphisms and the risk of fracture in each woman. The main finding was that of significant differences in the polymorphisms of the WNT16 rs2908004 genetic variant, notably, the less frequent presence of TC allele in women with a greater risk of osteoporotic fractures. We conclude that the polymorphism of the WNT16 gene seems highly relevant in the pathogenesis of osteoporosis, which makes it a promising object for further research on the genetic background of fracture risk.
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References
Albagha OME, Pettersson U, Stewart A, McGuigan FEA, MacDonald HM, Reid DM, Ralston SH (2005) Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone. J Med Genet 42:240–246
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 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 9:2043–2050
Bord S, Horner A, Beavan S, Compston J (2001) Estrogen receptors α and β are differentially expressed in developing human bone. J Clin Endocrinol Metab 86:2309–2314
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346(20):1513–1521
Colin EM, Uitterlinden AG, Meurs JBJ, Bergink AP, van de Klift M, Fang Y, Arp PP, Hofman A, van Leeuwen JPTM, Pols HAP (2003) Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk. J Clin Endocrinol Metab 88:3777–3784
Del Real A, Riancho-Zarrabeitia L, López-Delgado L, Riancho JA (2018) Epigenetics of skeletal diseases. Curr Osteoporos Rep 16(3):246–255
Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Antonarakis SE (2004) Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet 74:866–875
García-Ibarbia C, Pérez-Núñez MI, Olmos JM (2013) Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry, and fractures. Osteoporos Int 24(9):2449–2454
Ichikawa S, Koller DL, Peacock M, Johnson ML, Lai D, Hui SL, Johnston CC, Foroud TM, Econs MJ (2005) Polymorphisms in the estrogen receptor β (ESR2) gene are associated with bone mineral density in Caucasian men and women. J Clin Endocrinol Metab 90(11):5921–5927
Kanis JA, on behalf of the World Health Organisation Scientific Group (2007) Assessment of osteoporosis at the primary health care level. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield
Kanis JA, Oden A, Johansson H, Borgström F, Ström O, McCloskey E (2009) FRAX® and its applications to clinical practice. Bone 44:734–774
Koller DL, Zheng HF, Karasik D (2013) Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women. J Bone Miner Res 28(3):547–558
Lorentzon M, Mellstrom D, Ohlsson C (2005) Age of attainment of peak bone mass is site-specific in Swedish men―The GOOD Study. J Bone Miner Res 20:1223–1227
Mizuguchi T, Furuta I, Watanabe Y, Tsukamoto K, Tomita H, Tsujihata M, Ohta T, Kishino T, Matsumoto N, Minakami H, Niikawa N, Yoshiura K (2004) LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. J Hum Genet 49:80–86
Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene 492(1):1–18
Mozioğlu E, Akgöz M, Tamerler C, Kocagöz ZT (2014) A simple guanidinium isothiocyanate method for bacterial genomic DNA isolation. Turk J Biol 38:125–129
Ogawa S, Hosoi T, Shiraki M, Orimo H, Emi M, Muramatsu M, Ouchi Y, Inoue S (2000) Association of estrogen receptor β gene polymorphism with bone mineral density. Biochem Biophys Res Commun 269:537–541
Ralston SH, Uitterlinden AG (2010) Genetics of osteoporosis. Endocr Rev 31(5):629–662
Richards JB, Kavvoura FK, Rivadeneira F et al (2009) Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 151(8):528–537
Sowers M, Jannausch ML, Liang W, Willing M (2004) Estrogen receptor genotypes and their association with the 10-year changes in bone mineral density and osteocalcin concentrations. J Clin Endocrinol Metab 89:733–739
Stewart TL, Ralston SH (2000) Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol 166:235–245
van Meurs JB, Schuit SC, Weel AE, van der Klift M, Bergink AP, Arp PP, Colin EM, Fang Y, Hofman A, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG (2003) Association of 5-prime estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Hum Mol Genet 12:1745–1754
Zheng HF, Tobias JH, Duncan E et al (2012) WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet 8(7):e1002745
Zmuda JM, Cauley JA, Ferrell RE (1999) Recent progress in understanding the genetic susceptibility to osteoporosis. Genet Epidemiol 16:356–367
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The authors declare no conflicts of interest in relation to this article.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Mitek, T., Nagraba, Ł., Deszczyński, J., Stolarczyk, M., Kuchar, E., Stolarczyk, A. (2019). Genetic Predisposition for Osteoporosis and Fractures in Postmenopausal Women. In: Pokorski, M. (eds) Advancements and Innovations in Health Sciences. Advances in Experimental Medicine and Biology(), vol 1211. Springer, Cham. https://doi.org/10.1007/5584_2019_413
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DOI: https://doi.org/10.1007/5584_2019_413
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