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

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 入选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)70 mg每周1次及钙尔奇D 600 mg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-RFIP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(0.732±0.113)g/cm~2、(0.775±0.101)g/cm~2和(0.667 ±0.105)g/cm~2]均显著低于从基因型(0.819±0.157)g/cm~2、(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位点从基因型转子间骨密度变化百分比2.50(3.47)%]高于AG和GG基因型0.88(3.47)%,P=0.014];T245G位点TT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位点从基因型和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.

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

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/cm~2,(0.775±0.101)g/cm~2 vs(0.843±0.124)g/cm~2 and(0.667±0.105)g/cm~2 vs(0.725±0.091)g/cm~2].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~2 vs(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/cm~2 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 GG2.50(3.47)% vs 0.88%(3.47%)%,P=0.014].While at site T245G,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%) vs 0.89(3.01%),P=0.046].Concision The G allele of sites A163G and T245G may be the risk allele of postmenopausal osteoporosis.Furthermore, patients with genotypes AA (A163G)and(T245G)show a better therapeutic effect to alendronate.