Ongphiphadhanakul Boonsong
Division of Endocrinology and Metabolism, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Am J Pharmacogenomics. 2003;3(1):5-9.
Genetic factors play an important role in the determination of bone mass and osteoporosis. A number of candidate genes have been implicated in osteoporosis, including genes encoding type 1 collagen, vitamin D receptor, estrogen receptor-alpha (ERalpha), and others. A number of association studies have been performed with single nucleotide polymorphisms in the ERalpha gene to assess their relation with bone mineral density in pre- and postmenopausal women, as well as the rate of bone loss after menopause and skeletal response to estrogen administration. The polymorphisms studied thus far mostly involved intronic polymorphisms in intron 1. Other less frequently studied polymorphisms include those in exons 1, 4, and 8. Although most studies demonstrated associations with various bone-related parameters, the results are still disputed. Assessing genetic factors including ERalpha polymorphisms, if their significances are confirmed, can be helpful in targeting preventive measures to individuals with higher risk of developing osteoporosis and render the preventive effort more cost-effective. Moreover, pharmacogenetically, it may help identify postmenopausal women who tend to have better skeletal responses after estrogen replacement. It is not known, however, if patients who possess favorable polymorphisms in terms of skeletal responsiveness will also have an undesirably higher risk of adverse effects. This issue needs to be further investigated before clinical decisions based on the balance between benefits and risks can be made.
遗传因素在骨量和骨质疏松症的决定中起着重要作用。许多候选基因已被认为与骨质疏松症有关，包括编码1型胶原蛋白、维生素D受体、雌激素受体α（ERα）等的基因。已经对ERα基因中的单核苷酸多态性进行了多项关联研究，以评估它们与绝经前和绝经后妇女骨矿物质密度的关系，以及绝经后骨丢失率和骨骼对雌激素给药的反应。迄今为止研究的多态性大多涉及内含子1中的内含子多态性。其他较少研究的多态性包括外显子1、4和8中的多态性。尽管大多数研究表明与各种骨相关参数有关联，但结果仍存在争议。评估包括ERα多态性在内的遗传因素，如果其重要性得到证实，有助于针对患骨质疏松症风险较高的个体采取预防措施，并使预防工作更具成本效益。此外，从药物遗传学角度来看，它可能有助于识别绝经后雌激素替代后骨骼反应较好的女性。然而，尚不清楚在骨骼反应性方面具有有利多态性的患者是否也会有不良反应的高风险。在基于利弊平衡做出临床决策之前，这个问题需要进一步研究。
