- 學位論文
子宮內膜異位症與發炎基因多型性之相關
The role of cytokine and cytokine-related genes and the risk of adenomyosis and endometriosis
摘要
背景: 有越來越多的證據顯示發炎與子宮內膜異位症的生成有關。相對來說，發炎在子宮肌腺症的形成上所扮演的角色到目前為止還不確定。因此，本研究的目的就是為了探索發炎相關的細胞激素(IL-1β、IL-6、IL-10)和一個發炎相關基因(COX-2) 與子宮內膜異位症和子宮肌腺症之相關性。 方法: 本研究鑑定了153位只患有子宮內膜異位症、146位只患有子宮肌腺症及25位同時患有兩種疾病患者的基因型，這些病例組都經病理切片確診。此外，對照組有396位婦女，其中醫院來源的有162位、社區來源的則有234位。本研究所選的都是tSNPs，而且病例組和對照組都符合哈溫平衡。最後用多變量迴歸分析來評估基因作用及校正共變項，並且用Hap-Clustering 軟體來分析基因組單體型。 結果: 將子宮內膜異位症患者與對照組比較後發現位於IL-10 -819位置上的tSNP有達到統計上的意義，帶C對偶基因校正後的勝算比是0.58 (P=0.015)。另外，IL-10上的3個tSNPs的基因組單體型CCA也有很強的保護作用(P=0.0016)。至於其它3個基因，並沒有達到統計上的顯著意義。子宮肌腺症患者與對照組比較後，則沒任何基因有達到統計上的顯著意義。 結論:結果顯示出IL-10基因的多型性和子宮內膜異位症有很強的關聯，可是卻沒有發現和子宮肌腺症有任何的關係。而IL-10的基因組單體型則在子宮內膜異位症的生成上扮演著保護的角色。本研究的結果與現今子宮內膜異位症的致病機轉的理論有一致性，而子宮肌腺症則如預期所料，與發炎基因無相關性。
並列摘要
Background: Accumulating evidence implies inflammatory cytokines are involved in the development of endometriosis. On the contrary, the role of cytokines in adenomyosis is not well recognized. The aim of this study was to investigate the relationship between several cytokine genes and one cytokine related gene (IL-6, IL-10, IL-1B and Cox-2) and endometriosis and adenomyosis. Method: We genotyped 153 cases with only endometriosis, 146 cases with only adenomyosis and 25 cases with both diseases. The disease status was confirmed by pathology. Three hundreds and ninety-six disease-free controls including 162 enrolled at the hospital and 234 enrolled from the community were compared with either disease. We selected all the tagging single nucleotide polymorphisms (tSNPs) for Cox-2, IL-1B, IL-6 and IL-10. Hardy-Weinberg equilibrium was checked in both cases and controls. We used logistic regression to estimate the genetic effect and adjust the covariates. Hap-Clustering Program was performed for haplotype analysis. Result: When comparing endometriosis with controls, we found significant association between one IL-10 tSNP at the position -819 with an adjusted odds ratio of 0.58 (P=0.015) for the C allele carriers. Moreover, the haplotype CCA of 3 tSNPs at IL-10 showed a strong protective effect on the endometriosis susceptibility (P=0.0016). For the other three genes, we did not demonstrate significant association with endometriosis. For adenomyosis, none of the four candidate genes were found significant. Conclusion: Our data showed that IL-10 polymorphism was strongly associated with the risk of endometriosis but not adenomyosis. The haplotype of IL-10 may play a protective role on the development of endometriosis. Our result is consistent with the current concept of the pathogenesis of endometriosis. Our result also indicates that inflammatory genes may not be crucial for adenomyosis.