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LRP5 polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis Aim: To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women. Materials & methods: Six hundred and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were included and received alendronate treatment. The A1330V polymorphism of LRP5 was investigated. Bone mineral density (BMD) and bone turnover markers (ALP and b-isomerized carboxy-telopeptide of type I collagen [b-CTX]) were measured before and after treatment. The correlation of LRP5 polymorphisms with changes in BMD and bone turnover biomarkers were analyzed after treatment. Results: After 12 months of treatment, participants with CC and CT genotypes had a larger increase in lumbar spine BMD and a larger decrease in serum b-CTX and ALP levels than those with TT genotype (all p T), which leads to substitution of alanine by valine at position 1330 (p.Ala1330Val) in the extracellular region of LPR5. This region is responsible for modifying

the conformation and function of LRP5 and mediating the interactions of LRP5 and its ligands, thus rs3736228 of LRP5 has been a hot locus in correlation with BMD, fracture risk and response to treatment [9–13]. As we know, alendronate (ALN) has been widely used as the first-line treatment for osteo­ porosis because of its beneficial role in increasing bone mass and attenuating fracture risks in post­ menopausal osteoporotic women [14]. However, 8–25% of patients had a change in lumbar spine BMD less or equal to 0% after 2 years treat­ ment of ALN, risedronate or ibandronate [15]. Pharmacogenetics studies of osteoporosis have so far been insufficient; however, it is very useful to predict the effects of antiosteoporotic treat­ ment. Identification of nonresponse to bisphos­ phonates treatment is important to save medi­ cal expenditure. Studies in small size samples investigated the correlation between individual differences in response to antiresorptive treat­ ments and polymorphisms of the VDR or FDPS genes, but their results were controversial [16,17]. Although common genetic variants of LRP5 are possibly related to risks of osteoporosis, lit­ tle information is known about whether LRP5 variants affect the response to ALN treatment. Therefore, we investigated the relationship between a common encoding polymorphism of

10.2217/PGS.14.12 © 2014 Future Medicine Ltd

Pharmacogenomics (2014) 15(6), 821–831

Pei Ran Zhou‡, Hai Juan Liu‡, Er Yuan Liao, Zhen Lin Zhang, De Cai Chen, Jian Liu, Wen Wu, Xiao Ping Xing, Wei Bo Xia, Ling Xu & Mei Li* *Author for correspondence: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, China Tel.: +86 10 69155088 Fax: +86 10 69155088 [email protected] ‡ Authors contributed equally For a full list of affiliations, please see page 831

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ISSN 1462-2416

821

Research Article

Zhou, Liu, Liao et al.

LRP5, A1330V, and bone response to ALN in Chinese postmenopausal women with osteopenia or osteoporosis.

Materials & methods „„ Participants In this large sample, prospective, multicenter study, more than 2000 postmenopausal women were screened from seven clinical centers of China (Beijing, Changsha, Shanghai, Chengdu, Xi’an, Guangzhou and Haerbin). The inclusion criteria were: years since menopause >1 year; BMI between 18 and 35 kg/m2; T score of BMD at lumbar spine or femoral neck

LRP5 polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis.

To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women...
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