护骨素基因多态性与阿仑膦酸钠治疗绝经后骨质疏松骨密度变化的关系  

Osteoprotegerin gene polymorphism and therapeutic response to alendronate in postmenopausal women with osteoporosis

作　　者：汪纯[1] 何进卫[1] 秦跃娟[1] 张浩[1] 胡伟伟[1] 刘玉娟[1] 章振林[1] 

机构地区：[1]上海交通大学附属第六人民医院骨质疏松科骨代谢病和遗传研究室,200233

出　　处：《中华医学杂志》2009年第42期2958-2962,共5页National Medical Journal of China

基　　金：国家自然科学基金（30570891,30771019,30800387）;上海市科委优秀学科带头人计划资助项目（08XD1403000）

摘　　要：目的探讨护骨素（OPG）基因多态性是否与绝经后骨质疏松病人阿仑膦酸钠治疗后骨密度的变化有关，明确是否存在与疗效有关的基因型。方法人选80例绝经后骨质疏松病人，平均年龄（64．2±7．7）岁，口服阿仑膦酸钠（福善美）70mg每周1次及钙尔奇D600mg每天1次，治疗为期1年。治疗前后分别进行腰椎及髋部骨密度检测。并运用PCR—RFLP对护骨素基因启动子区域3个多态性位点：A163G、T245G和T950C进行分析。结果80例中的67例完成1年阿仑膦酸钠治疗，A163G位点G等位基因携带者（AG和GG基因型）治疗前骨密度腰椎、转子间和全髋[（n732±0．113）g／cm2、（0．775±0．101）g／cm^2和（0．667±0．105）g／cm^2]均显著低于AA基因型[（0．819±0．157）g／cm2、（0．843±0．124）g／cm^2和（0．725±0．091）g／cm^2]；T245G位点的G等位基因携带者（TG和GG基因型）治疗前骨密度腰椎、转子间和全髋[（0．723±0．111）g／cm^2、（0．776±0．102）g/cm^2和（0．670±0．109）g／cm^2]均显著低于TT基因型[（0．819±0．155）g／cm^2、（0．840±0．124）g／cm^2和（0．721±0．091）g／cm^2]。治疗1年后，A163G位点AA基因型转子问骨密度变化百分比[2．50（3．47）％]高于AG和GG基因型[0．88（3．47）％，P=0．014]；T245G位点啊基因型转子间及髋部骨密度变化百分比[2．50（3．41）％和2．72（2．68）％]高于TG和GG基因型[0．61（3．31）％和0．89（3．01）％]（P=0．011，P=0．046）。结论OPG基因A163G和T245G位点的G等位基因可能是绝经后骨质疏松的危险等位基因，而且A163G位点AA基因型和T245G位点TT基因型的绝经后妇女对阿仑膦酸钠治疗可能具有更好的疗效。Objective To investigate whether the polymorphism of osteoprotegerin （OPG） gene is associated with the change of BMD （bone mineral density） after alendronate therapy in postmenopausal women with osteoporosis and determine the correlation between genotypes and therapeutic effect. Methods Eighty postmenopausal osteoporotic patients were recruited with an average age of （ 64. 2 ± 7. 7 ） years old. Every patient took oral alendronate （Fosamax） 70 mg weekly and Caltrate 600 mg daily for 12 months. At pre- and post-treatment, BMD was measured at lumbar spine 2-4 and hip sites. PCR-RFLP was performed for three polymorphisms at the promoter site of OPG gene （A163G, T245G and T950C）. Results One-year therapy was accomplished in 67 patients. Patients with G allele （genotype AG and GG） of site A163G, the baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype AA [ （0. 732 ±0. 113） g/cm^2 vs （0. 819 ± 0. 157） g/cm2, （0. 775 ± 0. 101 ） g/cm2 vs （0. 843 ± 0. 124） g/cm2 and （0. 667 ± 0. 105）g/cm2 vs （0. 725 ±0. 091）g/cm2]. Patients with G allele （genotype TG and GG） of site T245G, baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype TT [ （0. 723 ±0. 111 ） g/cm^2vs （0.819 ±0.155）g/cm^2, （0.776 ±0.102）g/cm^2 vs （0.840±0.124）g/cm^2 and （0.670± 0. 109）g/cmz vs （0. 721 ± 0. 091 ）g,/cm^2 ]. After one-year therapy, at site A163G, the percentage of BMD change at inter-troche was higher in genotype AA than in genotypes AG and GG [2. 50（3.47）% vs 0. 88% （ 3.47% ） %, P = 0. 014%. While at site T245 G, the percentage of BMD change at inter-troche and total hip were higher in genotype TT than in genotype TG and GG 2. 50% （ 3. 47% ） vs 0. 61% （ 3. 31% ）, P=0.011; 2.72%（2.68%） vs0.89（3.01%）, P=0.046].Conclusion The Gallele of sites A163G and T245G may be the risk allele of postmenopausal osteoporosis. Furthermore, patients with genotypes AA （A163G） and （T245G） show

关 键 词：骨质疏松 绝经后 基因 阿仑膦酸钠 骨密度 

分 类 号：R686[医药卫生—骨科学]