"吸菸, IL-6基因多型性,及阿茲海默氏病之風險"

Abstract

背景 近年來的研究顯示，吸菸可能導致神經系統之發炎作用，因而增加阿茲海默氏病的風險。發炎反應之細胞激素，interleukin-6 (IL-6)，也與老化的過程有關聯性。然而，過去研究並無探討發炎基因的遺傳多型性是否會調控吸菸與阿茲海默氏病之關聯性。本篇研究除了分析吸菸與遺傳多型性IL-6基因之間的交互作用，並同時探討吸菸和其他血管危險因子之間的交互作用。 方法 本研究為病例對照組設計。從2007至2010年間，自三家位於大台北地區的教學醫院神經科門診招募了292位阿茲海默氏病。此外，在同一時期的時間，由健康檢查及在醫院服務的義工中招募了502位的健康對照組。本研究使用自填式問卷收集吸菸、二手菸暴露、及血管危險因子之資料。本研究選取IL-6兩個常見的 (frequency 5%) haplotype-tagging 單核苷酸多型性 (htSNPs)，以探討IL-6基因多型性與阿茲海默氏病之關係及與吸菸的交互作用。 結果 過去戒菸者及目前吸菸者其阿茲海默氏病的風險較未曾吸菸者高[adjusted odds ratio (AOR) = 2.54, 95% confidence interval (CI)=1.42-4.53]。根據Apolipoprotein E (ApoE)4對偶基因分層後，未帶有ApoE 4對偶基因者吸菸會顯著地增加阿茲海默症之風險(AOR=3.30, 95% CI=1.68-6.49)。根據IL-6基因多型性分層後，未帶有IL-6基因多型性者，吸菸會顯著地增加阿茲海默氏病之風險[IL-6rs1800796 variant carriers (AOR=2.84, 95% CI=1.33-6.09), rs1524107 variant carriers(AOR=3.09, 95% CI=1.43-6.68)]。 結論 吸菸會顯著地增加阿茲海默症之風險，尤其是未帶有ApoE 4對偶基因或未帶有IL-6基因多型性者。

Background. Recent studies suggested that smokers were at elevated or unchanged risk of Alzheimer’s disease (AD) via the process of neuroinflammation. Dysregulation of interleukin-6 (IL-6) has also been associated with aging process. However, limited studies have explored how sequence variants of inflammatory genes modify the association of active smoking and secondhand smoke (SHS) with AD. Methods. This was a case-control study. We recruited 292 AD patients from neurology clinic of 3 hospitals from November 2007 to July 2010. Controls (n=502) were recruited from health checkup and volunteers in the hospital during the same period of time. All participants were aged 60 or older. A self-reported questionnaire was administered to collect information on demography, years of smoking and exposure to SHS, and vascular risk factors. Two common (frequency > 5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) in IL6 were genotyped. This study examined the association between smoking (active smoking and SHS) and the risk of AD and how genetic polymorphisms of IL-6modified this association. Results. Ever smokers are significantly associated with an increased risk of AD [adjusted odds ratio (AOR) = 2.54, 95% confidence interval (CI)=1.42-4.53]. After stratification, the association remains significant in ApoE e4 non-carriers only (AOR=3.30, 95% CI=1.68-6.49).No association is observed for SHS or nicotine exposure. Ever smokers had significant risk of AD in IL-6rs1800796 variant carriers (AOR=2.84, 95% CI=1.33-6.09) and rs1524107 variant carriers(AOR=3.09, 95% CI=1.43-6.68). Conclusions. Active smoking is associated with an increased risk of AD, especially in ApoE e4 non-carriers and IL-6 variant non-carriers.