- 學位論文
台灣族群中PNPLA3 rs738409基因變異與肝硬化之相關性探討
Association between PNPLA3 rs738409 genetic variant and liver cirrhosis in Taiwanese population
摘要
研究背景與目的 (Background and Aims): 近年來，透過全基因組關聯分析(GWAS)，研究已證實了歐洲族群的PNPLA3 rs738409基因變異與肝硬化的發展有關;此外，亦揭示了歐洲非C型肝炎、C型肝炎族群中rs738409變異與肝硬化的發生具有相關。根據現有知識，尚無研究於亞洲進行探討，特別是台灣。故本研究旨在了解PNPLA3 rs738409基因與台灣族群肝硬化之間是否存在相關性，並闡明其於C型肝炎和非C型肝炎族群中是否亦然。 材料與方法 (Methods): 本研究使用台灣人體生物資料庫(Taiwan Biobank)基因與社會人口學資料以及台灣健保資料庫(NHIRD)全疾病資料(包含肝硬化與糖尿病)進行分析。研究樣本包含30至70歲，17712位台灣人。透過身分證字號進行資料庫串檔整合，並使用複邏輯斯迴歸(包括共顯性、附加、顯性與隱性模型) 分析一般族群、C型肝炎族群及非C型肝炎族群中rs738409與肝硬化之相關性（勝算比）。 結果 (Results): rs738409基因變異與肝硬化於共顯性模型 [0.91 (95%CI 0.67-1.26) for CG; 1.22 (95%CI 0.81-1.85) for GG] 、附加模型 [1.07 (95%CI 0.86-1.31)]、顯性模型 [0.99 (95%CI 0.73-1.32)] 及隱性模型 [1.28 (95% CI 0.88-1.88)] 中均無顯著之勝算比，在C型肝炎與非C型肝炎族群中結果亦然。此外，發現吸菸、B型肝炎、C型肝炎、糖尿病和膽紅素皆與肝硬化相關。 討論 (Conclusions): 本研究指出PNPLA3基因變異非台灣成人肝硬化之顯著危險因子，於C型肝炎、非C型肝炎族群中亦具相同結果。然而，未來仍需更多世代研究與臨床研究進行相關證實。
並列摘要
Background and Aims: Recently, genome-wide association studies (GWAS) have confirmed an association between PNPLA3 rs738409 genetic variant and liver cirrhosis progression in European individuals. In addition, it was also revealed that the relationship between rs738409 variant and cirrhosis development in HCV (hepatitis C virus) and non-HCV European population. To the best of our knowledge, no study has been conducted on the same association in Asia, especially in Taiwan. Therefore, in this study, we aimed to find out whether there is any association between PNPLA3 rs738409 and cirrhosis in Taiwanese population as well as to clarify the same association in HCV and non-HCV Taiwanese individuals. Methods: A total of 17712 Taiwanese participants aged 30-70 years were recruited in this study; genetic and sociodemographic information were collected from Taiwan Biobank database, while diseases (cirrhosis and diabetes) information were collected from the National health insurance research database of Taiwan. Both data were combined using personal identification’s number. Multivariate logistic regression (co-dominant, log-additive, dominant and recessive models) were applied to evaluate an association (odds ratios) between rs738409 and cirrhosis in general, non-HCV and HCV participants. Results: The rs738409 genetic variant did not show any significant odds ratio (OR) of liver cirrhosis in co-dominant [0.91 (95%CI 0.67-1.26) for CG; 1.22 (0.81-1.85) for GG], log-additive [1.07 (95%CI 0.86-1.31)], dominant [0.99 (95%CI 0.73-1.32)] and recessive models [1.28 (95% CI 0.88-1.88)]. Furthermore, the results also were not significant in non-HCV and HCV individuals. Besides, age, current smoking, HCV (hepatitis C virus), HBV (hepatitis B virus), diabetes and bilirubin showed significant association with liver cirrhosis. Conclusions: Our study suggests that PNPLA3 gene variant is not a significant risk factor for liver cirrhosis in Taiwanese adults, as well as in HCV positive and negative individuals. However, further cohort and clinical studies are still needed to confirm this association.
並列關鍵字
PNPLA3 gene variant ； rs738409 ； liver cirrhosis ； hepatitis C virus ； hepatitis B virus ； Taiwan.參考文獻
延伸閱讀
- Cherng, J. M., Tsai, T. C., Chiang, C. C., Wang, C. W., Chen, T. P., & Perng, D. S. (2009). NAD (P)H: QUINONE OXIDOREDUCTASE 1 (NQO1)C609T基因之多形性與臺灣肝癌之相關性. 臺灣消化醫學雜誌, 26(2), 156-163. https://doi.org/10.6557/GJT.200906_26(2).0003
- 張章裕（2005）。台灣健康人及肝癌病患對多種藥物抗藥性基因多型性變異之探討〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714541849
- 潘文正（2005）。台灣地區慢性C型肝炎病患與變形成長因子基因多形性之關係〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-2903200614023133
- 宋瑞樓（1997）。The Control of Liver Cirrhosis and Hepatocellular Carcinoma in Taiwan: Studies, Policies and Their Efficacy。台灣醫學，1(1)，1-11。https://doi.org/10.6320/FJM.1997.1(1).03
- 簡雪雁（2005）。Association Study of Gene Polymorphisms and Juvenile Allergic Diseases in Taiwan〔碩士論文，中山醫學大學〕。華藝線上圖書館。https://doi.org/10.6834/CSMU.2005.00045