Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density
Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density
复制标题
甲羟戊酸途径的基因多态性影响中国绝经后低骨密度女性对阿仑膦酸钠治疗的反应
DOI：
10.1038/tpj.2014.52
复制
发表时间：
2015-04-01
影响因子：
2.8
通讯作者：
Zhang, Z-L
中科院分区：
文献类型：
--
作者：
Wang, C.;Zheng, H.;Zhang, Z-L
阿仑膦酸钠是一种靶向甲羟戊酸途径的抗骨质疏松药物。为了研究这一通路的遗传变异是否影响阿仑膦酸钠在绝经后骨质疏松或骨质减少的中国妇女中的临床疗效，我们对500例服用阿仑膦酸钠12个月的患者进行了7个基因的23个单核苷酸多态性（snp）的基因分型。在基线和12个月后测量骨密度（BMD）。MVK 3 '侧区的rs10161126 SNP和FDFT1的GTCCA单倍型与治疗反应显著相关。在rs10161126的GG纯合子中，腰椎骨密度增加6.6%；AG杂合子和AA纯合子分别增加了4.4和4.5%。G等位基因携带者对腰椎骨密度有应答的比值比（95%可信区间）为2.06（1.08-6.41）。FDFT1中GTCCA单倍型在全髋关节应答组中比在无应答组中更频繁地被检测到（2.6% vs 0.5%， P= 0.009）。因此，MVK和FDFT1多态性是绝经后中国妇女对阿仑膦酸钠治疗的骨密度反应的遗传决定因素。
Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3′ flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08–6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P= 0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.