臺灣類風濕性關節炎全基因體關聯性研究

Abstract

背景：類風濕性關節炎是一種自體免疫疾病，主要特徵是慢性發炎性滑膜炎，而導致關節疼痛、僵硬、腫脹或扭曲，嚴重者可至失能，患者預期生存期比一般人口少了17年。類風濕性關節炎與遺傳基因有關，過去研究已經確定了超過100個風險位點；然而，雖然該風險位點存在著明顯的族群差異，過去多數相關研究僅以歐洲族群為分析對象。本研究目的為1)找出臺灣族群的類風濕性關節炎風險位點；2)將找出的臺灣族群類風濕性關節炎風險位點，以既有資料庫中的東亞族群與歐洲族群，比較兩者之間的風險位點差異。 方法：本研究樣本取自臺灣人體生物資料庫，共137位患者病例組，及對照組15,785人，控制類風濕性關節炎的危險因子(年齡、性別、有無類風濕性關節炎家族病史)影響後，使用羅吉斯迴歸模型估計與類風濕性關節炎有關的風險位點。將找出的臺灣族群類風濕性關節炎風險位點，以既有資料庫中的東亞族群與歐洲族群，進行信賴區間估計來找出兩者之間的風險位點差異。 結果：本研究共有604,202個單核苷酸多型性位點納入分析，共36個單核苷酸多型性位點與類風濕性關節炎顯著相關(p＜0.0001)。比對東亞族群與歐洲族群的風險位點資訊後，多數風險位點顯示在兩個族群中有明顯差異，除了其中5個風險位點。 結論：本研究結果在臺灣族群中發現特定的類風濕性關節炎風險位點，且這些位點多數有明顯的東亞與歐洲族群的差異。我們的結果顯示針對本土樣本探討特有的類風濕性關節炎風險位點是有必要性的，該研究發現將能夠有效應用於當地公共衛生與臨床醫療的發展及治療。

Introduction: Rheumatoid arthritis is an autoimmune disease, with the immune system losing its normal function and attacking normal tissues or organ in the body. The main feature of the disease is chronic inflammatory synovitis, which causes joint pain, stiffness, swelling or even disability. The patients’ expected survival time is 17 years shorter than the general population. It is known that most of rheumatoid arthritis is related to genetics and more than 100 risk sites have been identified. However, most of the known risk single nucleotide polymorphisms (SNPs) were identified in the European populations even the difference in risk SNPs between different ethnic groups were emphasized. The purposes of the study were i) to identify the risk SNPs of rheumatoid arthritis in the Taiwanese population; ii) to compare the differences of these risk SNPs between East Asian and European populations. Methods: A total of 137 rheumatoid arthritis cases and a control group of 15,785 were extracted from the Taiwan Biobank. A logistic regression model was used to evaluate the effect of risk SNPs after controlling for the covariates of rheumatoid arthritis including age, sex, and family history of rheumatoid arthritis. Besides, interval estimates were used to evaluate the difference in risk SNPs between the East Asian and the European populations using the GWAS Catalog database. Results: A total of 604,202 SNPs were included in the analysis, and 36 SNPs were significantly associated with rheumatoid arthritis (p <0.0001). After comparing the estimates of Asian and the European populations, there were marked differences between the two populations in most of the risk SNPs, with the exception of five out of them. Conclusions: Our findings identified some specific risk SNPs of rheumatoid arthritis in the Taiwanese population and supported it is essential to identify the risk SNPs of rheumatoid arthritis using local samples. Our findings could provide new insights into the development of rheumatoid arthritis in public health and clinical medicine.