雌激素受体α基因多态性与骨重塑标志物的变化及雌激素治疗反应相关。

Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen.

作者信息

Rapuri P B, Gallagher J C, Knezetic J A, Haynatzka V

机构信息

Bone Metabolism Unit, Creighton University, School of Medicine, 601 North 30th Street, Room 6718, Omaha, NE 68131, USA.

出版信息

Maturitas. 2006 Mar 20;53(4):371-9. doi: 10.1016/j.maturitas.2005.07.007. Epub 2005 Aug 31.

DOI:10.1016/j.maturitas.2005.07.007

PMID:16139450

Abstract

OBJECTIVES

Association studies between estrogen receptor alpha (ERalpha) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERalpha gene polymorphisms on BMD, biochemical markers, rates of bone loss and the response to estrogen/hormone therapy (ET/HT) in elderly postmenopausal women.

METHODS

At baseline, we measured the association between ERalpha genotypes and BMD and biochemical markers in 489 elderly women, mean age 71 +/- 3 years. In the longitudinal study, the changes in the same measures were determined in 96 women on placebo and in 79 women receiving the ET/HT for 3 years. The XbaI and PvuII ERalpha polymorphisms were determined by polymerase chain reaction (PCR). BMD measurements for spine, femoral neck and total body were performed by DEXA, and biochemical indices were measured by standard methods.

RESULTS

Neither the PvuII nor the XbaI ERalpha gene polymorphisms were associated with baseline BMD and biochemical indices. In the longitudinal study, there were trends for higher bone loss in the placebo group in the genotypes pp or xx compared to PP or XX genotypes, but the changes were not significant. However, the changes in the bone markers were significantly (p < 0.05) higher in genotype group pp compared to PP (serum osteocalcin, 4.9 +/- 7.0% versus -13.4 +/- 6.7%; urine NTx:Cr ratio, 32.3+/-10.3% versus -2.5 +/- 10.3%) or xx compared to XX (serum osteocalcin, 7.5 +/- 6.4% versus -15.6+/-7.3%; urine NTx:Cr ratio, 39.4 +/- 9.2% versus -8.84+/-10.7%). At the end of 3 years, the mean urine NTx:Cr ratio was 78.7 +/- 9.0 versus 44.6 +/- 4.9 in pp versus PP (p < 0.05) and 75.5 +/- 10.7 versus 48.7 +/- 5.4 in xx versus XX (p < 0.05) genotypes. The response in total body BMD to ET/HT treatment was significantly higher in women with the PP genotype compared to pp genotype (2.48 +/- 0.55% versus 0.66 +/- 0.46%). Similar trends were seen at other skeletal sites for both XX and PP compared to pp and xx genotypes.

CONCLUSION

Women with ERalpha, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy.

摘要

目的

雌激素受体α（ERα）基因多态性与骨密度（BMD）之间的关联研究结果并不一致。在本研究中，我们评估了XbaI和PvuII ERα基因多态性对老年绝经后女性骨密度、生化指标、骨质流失率以及雌激素/激素疗法（ET/HT）反应的影响。

方法

在基线时，我们测量了489名平均年龄为71±3岁的老年女性中ERα基因型与骨密度及生化指标之间的关联。在纵向研究中，测定了96名服用安慰剂的女性和79名接受ET/HT治疗3年的女性相同指标的变化。通过聚合酶链反应（PCR）确定XbaI和PvuII ERα基因多态性。采用双能X线吸收法（DEXA）测量脊柱、股骨颈和全身的骨密度，并通过标准方法测量生化指标。

结果

PvuII和XbaI ERα基因多态性均与基线骨密度和生化指标无关。在纵向研究中，与PP或XX基因型相比，pp或xx基因型的安慰剂组有骨质流失更高的趋势，但变化不显著。然而，与PP基因型相比，pp基因型组的骨标志物变化显著更高（血清骨钙素，4.9±7.0%对-13.4±6.7%；尿NTx:Cr比值，32.3±10.3%对-2.5±10.3%），与XX基因型相比，xx基因型的情况类似（血清骨钙素，7.5±6.4%对-15.6±7.3%；尿NTx:Cr比值，39.4±9.2%对-8.84±10.7%）。3年后，pp基因型与PP基因型相比，尿NTx:Cr平均比值为78.7±9.0对44.6±4.9（p<0.05），xx基因型与XX基因型相比为75.5±10.7对48.7±5.4（p<0.05）。与pp基因型相比，PP基因型的女性全身骨密度对ET/HT治疗的反应显著更高（2.48±0.55%对0.66±0.46%）。在其他骨骼部位，XX和PP基因型与pp和xx基因型相比也有类似趋势。