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

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題名:	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 Investigation of gene polymorphism in endometriosis development and impact of co-morbidity on endometriosis-related infertility
作者:	張穎宜;Cherry Yin-Yi Chang
貢獻者:	公共衛生學系博士班
關鍵詞:	子宮內膜異位症;基因多型性;共病;endometriosis;polymorphism;co-morbidity
日期:	2014-01-16
上傳時間:	2014-10-02 09:40:10 (UTC+8)
出版者:	中國醫藥大學
摘要:	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.
顯示於類別:	[公共衛生學系暨碩博班] 博碩士論文

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