Zheng Hui, Wang Chun, He Jin-Wei, Fu Wen-Zhen, Zhang Zhen-Lin
Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated the Sixth People's Hospital, Shanghai, People's Republic of China.
Pharmacogenet Genomics. 2016 Jan;26(1):12-9. doi: 10.1097/FPC.0000000000000181.
The aim of the study was to explore the association between OPG, RANKL, and RANK gene variations and the bone mineral density (BMD) response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia.
In the present study, 40 single-nucleotide polymorphisms (SNPs) in the OPG, RANKL, and RANK genes were genotyped in 501 postmenopausal Chinese women with osteoporosis or osteopenia who were given alendronate (70 mg weekly) orally for 1 year. The BMD at the lumbar spine 1-4 (L1-L4), femoral neck, and total hip was measured.
A total of 442 patients completed 1 year of alendronate therapy. The rs7239261 SNP of the RANK gene was significantly associated with baseline L1-L4 BMD (P=0.0004) after correction for age and BMI. Participants with the SNP A allele (C/A and A/A) had a higher BMD than those with the C/C genotype (C/A vs. C/C, P=0.001; A/A vs. C/C, P=0.025). Haplotypes AG of rs7239261-rs12969154, GG of rs3826619-rs11877530, and CACG of rs1805034-rs8083511-rs17069895-rs7231887 in the RANK gene were genetic protective factors toward a higher baseline L1-L4 BMD. No association was observed between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy.
The RANK gene might contribute to genetic variability in L1-L4 BMD in postmenopausal Chinese women with osteoporosis or osteopenia. No evidence of an association between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy was found in postmenopausal Chinese women with osteoporosis or osteopenia.
本研究旨在探讨绝经后中国骨质疏松或骨量减少女性中，骨保护素（OPG）、核因子κB受体活化因子配体（RANKL）和核因子κB受体活化因子（RANK）基因变异与阿仑膦酸钠治疗后骨密度（BMD）反应之间的关联。
在本研究中，对501例绝经后中国骨质疏松或骨量减少女性进行了OPG、RANKL和RANK基因中40个单核苷酸多态性（SNP）的基因分型，这些女性口服阿仑膦酸钠（每周70mg），为期1年。测量了第1-4腰椎（L1-L4）、股骨颈和全髋部的骨密度。
共有442例患者完成了1年的阿仑膦酸钠治疗。在校正年龄和体重指数后，RANK基因的rs7239261 SNP与基线L1-L4骨密度显著相关（P=0.0004）。携带SNP A等位基因（C/A和A/A）的参与者比携带C/C基因型的参与者骨密度更高（C/A与C/C相比，P=0.001；A/A与C/C相比，P=0.025）。RANK基因中rs7239261-rs12969154的单倍型AG、rs3826619-rs11877530的GG以及rs1805034-rs8083511-rs17069895-rs7231887的CACG是基线L1-L4骨密度较高的遗传保护因素。未观察到OPG、RANKL和RANK基因的任何SNP或单倍型与阿仑膦酸钠治疗后骨密度反应之间存在关联。
RANK基因可能导致绝经后中国骨质疏松或骨量减少女性L1-L4骨密度的遗传变异。在绝经后中国骨质疏松或骨量减少女性中，未发现OPG、RANKL和RANK基因的任何SNP或单倍型与阿仑膦酸钠治疗后骨密度反应之间存在关联的证据。
