广西壮族绝经后妇女雌激素受体-α基因多态性对血清护骨素的影响

Effect of estrogen receptor-α gene polymorphism on serum osteoprotegerin and calcaneus bone density in postmenopausal women in Guangxi Zhuang nationality

目的了解雌激素受体-α基因多态性对广西壮族绝经后妇女护骨素的影响,为雌激素受体基因所致的护骨素降低引起绝经后骨质疏松症早期防治提供理论依据。方法621例广西壮族绝经妇女,定量超声骨质密度仪检测右侧足跟骨测量宽带超声衰减值,并早上空腹采肘静脉血5 ml,限制性片段长度多态性聚合酶链反应(PCR-RFLP)检测雌激素受体-α基因多态性,用酶联免疫法测定各基因型对应的血清护骨素。结果绝经早期各雌激素受体-α各基因型的护骨素和骨密度都是降低的,各雌激素受体-α各基因型之间骨密度和护骨素均无明显差别(P>0.05)。而60岁后绝经晚期雌激素受体-αPvuⅡ酶切的P等位基因与同一年龄组其他4个基因组比较,护骨素和骨密度明显降低(P<0.05);65岁后绝经晚期雌激素受体-αXbaⅠ酶切的Xx等位基因与同一年龄组其他4个基因组比较,护骨素和骨密度明显提高(P<0.05)。结论雌激素受体-αPvuⅡ酶切的P等位基因护骨素和骨密度较低,更易患绝经后骨质疏松症,而雌激素受体-αXbaⅠ酶切的Xx等位基因护骨素和骨密度较高,不易患绝经后骨质疏松症。绝经后骨质疏松症防治方面,应该根据雌激素受体不同基因型对不同个体采取个体化防治。

Objective To investigate the effect of estrogen receptor-α gene polymorphism on osteoprotegerin(OPG)and calcaneus bone density in early and late postmenopausal women in Guangxi Zhuang nationality, in order to provide the theoretical basis for the early prevention and treatment of postmenopausal osteoporosis caused by estrogen receptor gene-induced osteoprotegerin reduction. Methods The broadband ultrasound attenuation in the right heel bone was measured by quantitative ultrasound bone densitometry in 621 postmenopausal women of Guangxi Zhuang nationality.Peripheral blood mononuclear cells and their DNA were extracted.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to detect the estrogen receptor-α gene polymorphism.Serum osteoprotegerin level was determined by enzyme-linked immunosorbent assay.The differences of data distribution of OPG and calcaneus bone density were compared between five items of 3 genotypes and 2 alleles at the same age group of 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-80 years. Results Women aged 60 years and over versus those aged 40-59 years showed that serum osteoprotegerin(OPG)and bone mineral density(BMD)were decreased(P<0.05), and had no significant difference among allele P, p, genotype Pp, pp, PP of ER-α Puv-Ⅱ polymorphism at the same age groups(P>0.05). Women aged 60 years and over showed that ER-α Puv Ⅱ polymorphism of allele big P versus p, Pp, pp, PP in the same age groups had significantly decreased serum osteoprotegerin and bone mineral density.Women aged 65 years and over showed that ER-α XbaⅠpolymorphism of heterozygote Xx versus xx, XX, X, x in the same age groups had a significantly increased serum osteoprotegerin and bone mineral density(P<0.05). Conclusions Women with big P allele of ER-α PvuⅡpolymorphism have low serum osteoprotegerin level and a decreased bone mineral density, who are prone to postmenopausal osteoporosis.Thus, P allele of ER-α PvuⅡpolymorphism is a causative agent.More attention should be paid to early prevention and treatment.But, women with the Xx heterozygote of ER-α XbaⅠpolymorphism have high serum osteoprotegerin level and an increased bone mineral density, who are not easy to suffer from postmenopausal osteoporosis.Therefore, Xx heterozygote of ER-α XbaⅠpolymorphism is a protective agent.The prevention and treatment of postmenopausal osteoporosis should be individualized based on estrogen receptor-α gene polymorphism.