Department of Obstetrics and Gynecology, Incheon Medical Center, Seoul National University, Seoul, Korea.
Menopause. 2011 Jul;18(7):808-13. doi: 10.1097/gme.0b013e318208f9b2.
The aim of this study was to explore the association between Wnt signaling pathway gene polymorphisms and response to hormone therapy (HT) as related to bone mineral density (BMD) in postmenopausal Korean women.
The BMD and serum levels of osteoprotegerin, the soluble receptor activator of the nuclear factor κB ligand, and bone turnover markers were measured in 308 postmenopausal women receiving sequential estrogen + progestogen therapy. Results were analyzed according to the low-density lipoprotein receptor--related protein (LRP5) 5 c.266A > G, c.3893C > T, frizzled receptor 6 gene c.1033A > C, axin II c.148C > T, adenomatous polyposis coli c.5645T > A, and T-cell factor 1 c.766G > A polymorphisms.
The rates of 1-year changes in BMD and changes at 6 months in osteoprotegerin, soluble receptor activator of the nuclear factor κB ligand, and bone turnover markers after HT did not differ significantly between all single and haplotype genotypes of the genes studied. When a nonresponder was defined as a woman who had lost more than 3% of BMD per year after HT, women with T allele of the LRP5 c.3893C > T polymorphism showed a significantly higher risk of nonresponse at both the lumbar spine and femoral neck than did women with C allele. The risk of nonresponse at the lumbar spine was significantly higher in women with G allele of the LRP5 c.266A > G polymorphism than that in women with A allele, and the c.266G/c.3893T (GT) haplotype allele showed a similar trend.
The LRP5 c.266A > G and c.3893C > T polymorphisms may be associated with risk of nonresponse to HT in postmenopausal Korean women.
本研究旨在探讨 Wnt 信号通路基因多态性与激素治疗（HT）反应之间的关联，以及其与绝经后韩国女性骨密度（BMD）的关系。
对 308 例接受序贯雌激素+孕激素治疗的绝经后妇女进行 BMD 及血清骨保护素、核因子 κB 配体可溶性受体激活剂和骨转换标志物水平检测。根据低密度脂蛋白受体相关蛋白（LRP5）5c.266A>G、c.3893C>T、卷曲受体 6 基因 c.1033A>C、轴突抑制因子 II c.148C>T、结肠腺瘤性息肉病 c.5645T>A 和 T 细胞因子 1 c.766G>A 多态性对结果进行分析。
所有基因单核苷酸多态性和单倍型基因型的患者在 HT 后 1 年 BMD 变化率及 6 个月时骨保护素、核因子 κB 配体可溶性受体激活剂和骨转换标志物的变化无显著差异。将每年 BMD 丢失超过 3%的患者定义为无反应者，LRP5 c.3893C>T 多态性 T 等位基因携带者在腰椎和股骨颈的无反应风险明显高于 C 等位基因携带者。LRP5 c.266A>G 多态性 G 等位基因携带者在腰椎的无反应风险明显高于 A 等位基因携带者，c.266G/c.3893T（GT）单倍型等位基因也表现出类似的趋势。
LRP5 c.266A>G 和 c.3893C>T 多态性可能与绝经后韩国女性 HT 无反应的风险相关。
