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研究生:張穎宜
研究生(外文):Cherry Yin-Yi Chang
論文名稱:子宮內膜異位病人之基因多型性對疾病發生及共病對不孕症發生之探討
論文名稱(外文):Investigation of gene polymorphism in endometriosis development and impact of co-morbidity on endometriosis-related infertility
指導教授:宋鴻樟宋鴻樟引用關係
指導教授(外文):Fung-Chang Sung
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:公共衛生學系博士班
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:56
中文關鍵詞:子宮內膜異位症基因多型性共病
外文關鍵詞:endometriosispolymorphismco-morbidity
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子宮內膜異位症是女性常見的婦科疾病,大約有10%的育齡的婦女會罹患子宮內膜異位症這個疾病。在臨床上子宮內膜異位症可能會有痛經,骨盆腔沾粘、不孕症及卵巢癌的情形出現。但子宮內膜異位症真正的病理機制目前並不清楚。 黏液素是一種高分子量的醣蛋白,它被認為與免疫功能、癌症的發生與進展及生殖有關。因此黏液素可能與子宮內膜異位症的形成、癌症的進展或者不孕的形成有某種程度的關連性存在。在臨床上有許多疾病彼此之間是有相關的,也會彼此互相影響。例如糖尿病,高血壓與心臟血管疾病。在這個研究中, 我們的研究結果顯示MUC2的基因多型性(rs10794288和rs10902088)與子宮內膜異位症相關的不孕症有關。MUC4的rs882605的T/G基因型與rs882605和rs1104760的T-T單倍體與子宮內膜異位症的發生有關。而rs882605的G等位基因與子宮內膜異位症相關的不孕症有關。然而MUC2和MUC4如何在子宮內膜異位症及與子宮內膜異位症相關的不孕症的病生理學中發揮作用的機制尚待闡明。而我們也利用台灣健保資料庫來探討子宮內膜異位症對不孕症的風險做分析,依據年齡及診斷日做配對,收集了5088位子宮內膜異位症及25440位沒有子宮內膜異位症的女性做追蹤,而資料顯示,相較於沒有子宮內膜異位症的患者,子宮內膜異位症的患者不孕的危險增加2.66倍(15.04 vs. 5.65 每 1000 人-年)。而其中,年輕的子宮內膜異位症患者有較高的比例有不孕的問題,而骨盆腔發炎和子宮外孕會讓不孕的風險更加提高,分別是2.15倍(95% 信賴區間 = 1.18-2.56)與2.07倍(95% 信賴區間 = 1.31-3.27)。

Endometriosis is a common gynecologic disease. Approximately, 10% females encounter the disease in their premenopausal ages. The common symptoms of endometriosis include pelvic pain, pelvic adhesion, infertility and abnormal menstruation. Approximatel 1% of endometriosis patients may subsequently develop ovarian cancer. However, the pathophysiology of endometriosis is unclear. Mucins (MUC) are high-molecular weight glycoproteins with function of lubricating and protecting epithelium and regarded to be related to modulation of immunity, reproduction and progress of tumor. Endometriosis and other comorbidities have been associated with infertility. At clinical settings, we recruited a group of women with endometriosis and a group of healthy women without the disease to investigate the association between endometriosis and polymorphisms of mucin-2 (MUC2) and mucin-4 (MUC4). Results showed that MUC2 polymorphisms, especially rs10794288 and rs10902088, were associated with endometriosis as well as endometriosis-related infertility (p = 0.030 and 0.013, respectively). In MUC4, both the T/G genotype of rs882605 and the frequency of haplotype T-T (rs882605 and rs1104760) were significantly higher in patients with endometriosis than in controls and were statistically significant (p = 0.04 and 0.035, respectively). The G allele at rs882605 was verified as a key genetic factor for infertility in patients.
This dissertation work also performed a study using Taiwan insurance claims data to investigate the association between endometriosis and the risk of infertility with a cohort of 5088 women with endometriosis and 25440 women without the disease frequency matched by age and diagnosis year. The overall incidence density of infertility was 2.66 times higher in the endometriosis cohort than in the comparison cohort (15.04 vs. 5.65 per 1000 person-years). Pelvic inflammatory disease increased the risk of infertility with an adjusted hazard ratio (HR) of 2.15 (95% confidence interval (CI) = 1.81-2.56) and ectopic pregnancy increased the risk of infertility with an adjusted HR of 2.07 (95% CI = 1.31-3.27).
In conclusion, MUC4 polymorphisms are associated with endometriosis development and endometriosis-related infertility in the Taiwanese population. Patients with endometriosis have higher risk to have infertility, pelvic inflammatory disease and ectopic pregnancy compared to the patients without endometriosis. In addition, the incidence of infertility is increased if patient with endometriosis has comorbidity of pelvic inflammatory disease or ectopic pregnancy.


致謝………………………………………………………………………………………………..I
中文摘要………………………………………………………………………………………….II
英文摘要…………………………………………………………………………………………IV
表目錄……………………………………………………………………………………………VI
圖目錄…………………………………………………………………………………………...VII
第一章 緒論
第一節 研究背景與研究動機……………………………………………………………..…1
第二節 研究的重要性……………………………………………………..…………………2
第三節 研究目的…………………………………………………………………..…………3
第四節 研究問題與研究假設……………………………………………………..…………4
第五節 名詞界定…………………………………………………………………..…………4
第二章 文獻查證
第一節 子宮內膜異位症……………………………………………………………..………5
第二節 子宮內膜異位症與黏液素……………………………………………………..……7
第三節 子宮內膜異位症與不孕症…………………………………...………………..…….8
第四節 研究架構……………………………………………………………………....……10
第三章 研究方法
研究目的一
第一節 研究設計………………………………………………………………………........11
第二節 研究對象………………………………………………………………………........11
第三節 研究工具的擬定………………………………………………………….....……...12
第四節 資料收集過程…………...……………………………………………………….....13
第五節 資料統計與分析…………………………………………………………………....14
研究目的二
第一節 研究設計…………………………………………………………………………....16
第二節 研究對象………………………………………………………………………..…..16
第三節 研究工具的擬定………………………………………………………………..…..17
第四節 研究世代的建置…………………………………………………………………..…..17
第五節 資料統計與分析………………………………………………………………..…..18
第四章 研究結果
研究目的一…………………………………………………………………………..………19
研究目的二……………………………………………………………………………..……25
第五章 討論
研究目的一………………………………………………………………………………..…27
研究目的二……………………………………………………………………………..……31
第六章 結論與建議
第一節 結論……………………………………………………………………….……..….33
第二節 研究限制………………………………………………………………………..…..33
第三節 應用與建議………………………..………………………………………………..34
參考文獻…………………………………………………………………………………………35
附錄…………………………………………………………………………………………43

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