Genetics and pharmacogenetics of osteoporosis

Czech version

Authors: Ivana Žofková ¹; Radoslav Omelka ²
Authors‘ workplace: Endokrinologický ústav Praha, ředitelka doc. RNDr. Běla Bendlová, CSc. ¹; Katedra botaniky a genetiky Fakulty prírodných vied Univerzity Konštantína Filozofa Nitra, Slovenská republika, vedúci katedry doc. RNDr. Roman Kuna, PhD. ²
Published in: Vnitř Lék 2014; 60(7-8): 575-581
Category: Reviews

Overview

Osteoporosis is a serious disease characterized by high morbidity and mortality due to atraumatic fractures. In pathogenesis of osteoporosis, except environment, internal factors, such as hormonal dysbalance and genetic background, are also in play. In this review, candidate genes for osteoporosis are classified accorging to metabolic or hormonal pathways, which regulate bone mineral density/and or quality (estrogen, RANKL/RANK/OPG, mevalonate, Wnt circuit, genes for collagen and vitamin D). Authors discuss the perspectives of practical utilization of pharmacogenetics (identification of single candidate genes using PCR) or pharmacogenomics (using genome wide association studies) in choise of optimal treatment of osteoporosis. Potentional predictors of effectivity of antiresorption therapy are genes ER, FDPS, Cyp19A1, VDR, Col1A1 and gene of Wnt pathway. Moreover, polymorphisms of CYP2C gene, but also FDPS may identify patients with high risk of undesirable effects of bisphosphonates (osteonecrosis of jaw). Unfortunately, results of the most association studies has not been confirmed by other investigators. The controversial results could be explained by different methodic approches in individual studies (different sample size, homogenity of investigated groups, ethnic differences or linkage disquilibrium between genes). Key cliff of association studies is low variability (7-10 %) of bone phenotypes associated with investigated genes. Nevertheless, identification of new genes and verification their association with bone denzity and/or quality using both PCR and genome wide association studies remain to be a great challenge targeting optimal prevention and treatment of osteoporosis.

Key words:
calcitonin – candidate genes for osteoporosis – osteoporosis – pharmacogenetics of osteoporosis – vitamin D

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