影响绝经后妇女骨密度变化的候选基因研究

Study of the impact of candidate genes on bone mineral density in postmenopausal women

目的探讨有关候选基因对绝经后妇女骨密度变化的影响。方法对205例绝经后妇女,应用双能X线骨密度仪测定腰椎和股骨颈骨密度。采用PCR测序法,检测护骨素基因多态性;采用PCR-限制性片段长度多态性方法,检测甲状旁腺激素、降钙素受体、骨钙素及瘦素受体基因多态性;采用PCR-琼脂糖凝胶电泳法,检测瘦素基因多态性。结果在护骨素基因第1外显子中,发现1个G-1181C单核苷酸多态性。在校正年龄及体重指数对骨密度的影响后,携带护骨素基因CC型及甲状旁腺激素基因bb型妇女的腰椎骨密度较高,分别为(1.042±0.142)g/cm2及(1.196±0.133)g/cm2。降钙素受体、骨钙素、瘦素及瘦素受体基因与骨密度之间无相关关系。经多元逐步回归分析,护骨素、甲状旁腺激素及骨钙素基因与腰椎骨密度变异有关,甲状旁腺激素基因与股骨颈骨密度的变异有关。结论护骨素及甲状旁腺激素基因与绝经后妇女骨量变异有一定关系,降钙素受体、骨钙素、瘦素及瘦素受体基因与绝经后妇女骨密度变异无关。护骨素基因可能是绝经后妇女发生骨量减少的遗传性标记。

Objective To investigate the impact of multiple candidate genes on bone mineral density in postmenopausal women. Methods Bone mineral density （BMD） at lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry （DEXA） in 205 postmenopausal women. Polymerase chain reaction （PCR） and direct sequencing technique were used to identify osteoprotegerin gene polymorphism. Parathyroid hormone, calcitonin receptor, osteocalcin and leptin receptor genes were evaluated through PCR and restriction fragment length polymorphisnm. Leptin gene was genotyped by PCR and agarose electrophoresis. Results One G-1181C single nucleotide polymorphism was found in the first exon of the osteoprotegerin gene. After adjustment for age and body mass index, women who were with the CC genotype of osteoprotegerin gene or the bb genotype of parathyroid hormone gene had the highest BMD value at the lumbar spine, which was （ 1. 042 ± 0. 142 ） g/cm^2 and （ 1. 196 ± 0. 133 ） g/cm^2, respectively. No association was found among calcitonin receptor, osteocalcin, leptin and leptin receptor genes with BMD in postmenopansal women. Multivariate regression analysis found that the osteoprotegerin, parathyroid hormone and osteocalcin genes associated with the variance of BMD at the lumbar spine, and the parathyroid gene associated with the variance of BMD at the femoral neck. Conclusions There is some association between osteoprotegerin, parathyroid hormone genes and BMD in postmenopausal women. However, no relationship has been found among calcitonin receptor, osteocalcin, leptin and leptin receptor genes with BMD in postmenopausal women. The osteoprotegerin gene may be the useful genetic marker for osteopenia in postmenopansal women.