探討B型肝炎帶原者週邊血液PPARs基因表現與代謝因子、肝臟異常的關係

Abstract

背景:研究顯示過氧化體增生活化受體(peroxisome proliferator-activated receptors, PPARs)的基因表現在調控脂質、血糖代謝與發炎反應扮演重要的角色。近期研究證實使用PPARs配體能有效治療非酒精性脂肪肝。 本研究目的為描述肝臟相關疾病的高危險群B型肝炎帶原者其週邊血液單核細胞之PPARs基因表現、代謝因子與肝臟異常的關聯性。 材料與方法：從1989年至1992年間招募的公務員世代中，選取共372位男性B型肝炎帶原者為研究對象。研究個案之糖尿病、BMI與血中轉氨酶於1989年進入研究時、追蹤期間和測量基因表現時量測；腰臀比與肝臟超音檢查則於追蹤期間與測量基因表現時被測定。本研究利用定量反轉錄聚合酶鏈反應分析PPARs於PBMCs的表現，並且以各個PPARs基因表現的中位數為切點將研究個案分為基因表現高和低兩組。最後用邏輯式迴歸分析PPARs基因表現、代謝因子和肝臟異常之間的關係。 研究結果：PPARα、PPARβ與PPARγ基因表現低與過重(BMI≧25 kg/m2)、腰臀比≧0.9和糖尿病等代謝因子呈顯著相關。此外，PPARα、PPARβ基因表現低皆和經肝臟超音波確診的肝硬化達顯著相關。經過年齡、抽菸、飲酒習慣、糖尿病與肝生化指標校正後，PPARα、PPARβ基因表現低其肝硬化的風險各為2.995 (95% CI:1.133-7.917)和2.730 (95% CI:1.010-7.379)。 結論：在B型肝炎帶原者中，週邊血液PPARs的基因表現量低為糖尿病的表徵，其相關條件可能與後期的肝臟疾病肝硬化有關。

Background: Studies have shown that peroxisome proliferator-activated receptors (PPARs) gene expression plays a critical role in lipid regulation, glucose metabolism and inflammation. The use of PPARs ligands was recently proved to be effective for treating non-alcoholic fatty liver disease. The aim of this study was to delineate the association between PPARs gene expression in peripheral blood mononuclear cells (PBMCs), metabolic factors and a spectrum of liver abnormalities among men with hepatitis B, who are at an extremely high risk of liver-related mortality. Materials and Methods: The study subjects included a total of 372 male hepatitis B carriers, belonging to a cohort study of civil servants recruited in 1989-1992. History of diabetes mellitus (DM), body mass index (BMI) and blood transaminase were measured at study subjects’ enrollment into the cohort since 1989 and at follow-up and measurement of gene expression, while waist-to-hip ratio and ultrasonographic liver abnormalities were determined at follow-up and measurement of gene expression. We determined expression levels of PPARs in PBMCs by quantitative reverse transcription polymerase chain reaction. The median of each PPAR expression level was used as the cutoff point to categorize the subjects into “high” and “low” expression groups. Logistic regression was used to analyze the relationship between PPARs gene expression, metabolic factors, and liver abnormalities. Results: Low PPARs gene expression were significantly associated with metabolic factors including overweight (BMI≧25 kg/m2), waist-hip ratio≧0.9 and prior DM. Furthermore, low expression of PPARα and PPARβ were significantly associated with liver cirrhosis detected by abdominal ultrasonography. After adjustment for age, cigarette smoking, alcohol consumption, DM, liver biochemical values, the odds ratio of liver cirrhosis was 2.995 (95% CI: 1.133-7.917) for low PPARα expression and 2.730 (95% CI: 1.010-7.379) for low PPARβ expression. Conclusion: Low peripheral expression of PPARs that characterize DM and related conditions might be associated with advanced liver disease such as liver cirrhosis in hepatitis B carriers.