- 學位論文
雌激素受體ERα mRNA重要性高於E2且可作為更年期婦女骨質疏鬆的生物指標
Estrogen Receptor α mRNA important than E2 Is an Independent biomarker for Postmenopausal Osteoporosis
摘要
研究目的：本研究主要在探討骨質疏鬆的評估及治療，骨質疏鬆是一種症狀不明顯，但是會持續進展的疾病，患者隨著人口的老化而逐漸增加。再加上近年來醫療照護進步，這些患者的平均壽命會比以前的人更長，因此骨質疏鬆症患者佔人口的比率也就日漸增加。骨質疏鬆症患者可預期其骨折風險會增加，而且骨質疏鬆症也常在骨折後才被診斷出來，因此，如何及早診斷出骨質疏鬆，提早治療來降低骨折風險是本研究的主要目的。 研究方法及材料：在本研究中包含86位45歲以上停經婦女，稱為停經組；另有86位25至45歲月經正常的婦女，稱為育齡組。利用用定量即時反轉錄聚合酶鏈反應(quantitative real-time reverse-transcription polymerase chain reaction; QRT-PCR)分析周邊血液淋巴球(peripheral blood lymphocytes; PBLs)中ERα mRNA的濃度，以及利用酵素連結免疫吸附測定(enzyme-linked immunosorbent assay; ELISA)來偵測血清中的雌二醇。 研究結果：本研究發現停經組中ERα mRNA在周邊血液淋巴球中的濃度與年齡呈現負相關，而與髖部和腰椎的T-scores為正相關，但在育齡組中則無如此的關聯性。此外，多變量分析的結果顯示，高齡（≥50歲）、低濃度的雌二醇(<45.6 pg/mL)、及周邊血液淋巴球中較低濃度的ERα mRNA (<200 copies/μg DNA)將可能各增加46.8、5.41及50倍的骨質疏鬆風險。 結論與建議：我們的結論是周邊血液淋巴球中ERα mRNA的濃度可單獨用來當作停經後骨質疏鬆的危險因子，而且它比年齡及血清中的雌二醇濃度等二項因子更具重要性。
並列摘要
Objective：Up- and down-regulation of the osteoclastogenesis response depends on the Estrogen/estrogen receptor (ER) signaling pathway. Previous reports have shown that promoter hypermethylation and gene polymorphism of ER α are risks for menopausal osteoporosis. No previous study has evaluated expression levels of ERα mRNA of menopausal osteoporosis using human subjects. We hypothesized that ERα mRNA expression may show less resistance to postmenopausal osteoporosis. Methods and Materials：In this study, we enrolled 86 women older than 45 years without menstruation and classified them as the menopausal group and classified another 86 women aged 25 to 45 years with regular menstruation as the childbearing age group. ERα mRNA levels in peripheral blood lymphocytes (PBLs) were analyzed by the quantitative real-time reverse-transcription polymerase chain reaction (QRT-PCR), and estrogen in serum was detected by ELISA. Results：We found that ERα mRNA levels in PBLs had a negative correlation with age and a positive correlation with hip and lumbar T-scores in the menopausal group but not in the childbearing age group. Additionally, multivariate analysis showed that older age (≥50 years), a low estradiol concentration (<45.6 pg/mL), and low ERα mRNA levels in PBLs (<200 copies/μg DNA) were associated with an approximately 46.80-, 5.41-, and 50-fold risk of osteoporosis. Conclusion：We conclude that ERα mRNA levels in PBLs could be used as an independent risk factor for menopausal osteoporosis and that they may be more important than age and serum estrogen levels.