骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松症女性骨密度和骨转换标志物影响的相关性

Association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis.

作者信息

Zhang Zhen-lin, He Jin-wei, Qin Yue-juan, Huang Qi-ren, Liu Yu-juan, Hu Yun-qiu, Li Miao

机构信息

Center for Preventing and Treating Osteoporosis, Osteoporosis Research Unit, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233 P.R.China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006 Apr;23(2):129-33.

PMID:16604479

Abstract

OBJECTIVE

To investigate the association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral density (BMD) and bone turnover markers in postmenopausal women with osteoporosis.

METHODS

A total of 68 unrelated postmenopausal women with osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2 groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo group. BMD and bone turnover markers were measured at baseline, 6 and 12 months after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor 1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding sites in vitamin D receptor gene (VDR) were analyzed.

RESULTS

A total of 58 patients completed 12 months of study period. By the end of study, the increased percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were found significantly different between RLX group and placebo group(P<0.05), and the decreased percentage of C-telopeptide and osteocalcin were significantly different between the two groups (P<0.01). The BMD of total hip and trochanter of women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and 2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%, respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association was observed of the polymorphisms of five sites with the changes of BMD and bone turnover markers in the placebo group.

CONCLUSION

The effect of RLX on BMD in postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug according to genotype of patients in clinical.

摘要

目的

探讨骨代谢相关基因多态性与盐酸雷洛昔芬（RLX）对绝经后骨质疏松症女性骨密度（BMD）及骨转换标志物影响之间的关联。

方法

将68例年龄47 - 74岁、无亲缘关系的汉族绝经后骨质疏松症女性随机分为两组，每组34例：RLX组（每日给予60 mg，共12个月）和安慰剂组。在治疗基线、治疗后6个月和12个月时测量BMD及骨转换标志物。分析雌激素受体1基因（ESR1）的Xba I和Pvu II位点、ESR2基因的Ras I位点以及维生素D受体基因（VDR）的起始密码子（Fok I）和CDX2结合位点的多态性。

结果

共有58例患者完成了12个月的研究期。研究结束时，RLX组与安慰剂组相比，腰椎2 - 4（L2 - 4）、全髋和大转子处BMD增加的百分比差异有统计学意义（P<0.05），两组间C - 端肽和骨钙素降低的百分比差异有统计学意义（P<0.01）。在RLX组中，VDR Fok I位点为FF基因型的女性全髋和大转子处的BMD分别降低了1.98%±4.86%和2.26%±4.73%，而Ff/ff基因型的女性则分别增加了2.52%±2.75%和2.74%±2.97%（P<0.05）。此外，ESR1 Pvu II位点为PP/Pp基因型的女性全髋BMD增加了2.12%±2.78%，而pp基因型的女性则降低了1.34%±3.73%（P<0.05）。然而，在安慰剂组中，五个位点的多态性与BMD和骨转换标志物的变化之间未观察到显著关联。