Clusterin基因多型性與阿茲海默症風險之關聯研究

Abstract

背景. Clusterin (CLU)在阿茲海默症的致病機轉中可能和脂質代謝和類澱粉斑(Aβ)的清除有關。近期的全基因關聯研究發現CLU基因與阿茲海默症風險有相關。 方法. 自2007到2010年間，我們以病例對照的研究，在三間教學醫院的神經內科門診招募278位阿茲海默症患者，同一時間內，另招募422位來自醫院的志工與參加老人健康檢查之民眾做為對照組。本研究共挑選了4個常見的(對偶基因頻率> 5%) haplotype-tagging單核苷酸多型性(htSNP)來分析CLU基因多型性與阿茲海默症的關聯。為了探討CLU基因多型性與ApoE ε4對偶基因、性別以及高血壓的交互作用對阿茲海默症風險之影響，另進行分層分析。 結果. 研究結果顯示帶有rs11136000變異的對偶基因會降低阿茲海默症風險[2 vs. 0 copies: odds ratio (OR) = 0.17, 95% confidence interval (CI) = 0.05-0.60]。由所選的4個htSNP組成的常見的單倍體(haplotype)，共有5個(累積頻率為95.9%)，其中帶有兩個變異的單倍體TATT會顯著降低阿茲海默症風險(2 vs. 0 copies: OR = 0.19, 95% CI = 0.05-0.66)。我們也發現CLU單倍體與高血壓有交互作用存在(P值為0.04)。 結論. 此研究發現CLU基因多型性與阿茲海默症風險有關，這些遺傳標記可做為阿茲海默症的重要預測因子。

Background. Clusterin (CLU) is involved in lipid metabolism and beta amyloid (Aβ) clearance, which have been related to the pathogenesis of Alzheimer’s disease (AD). Recent genome-wide association studies have found that CLU genetic polymorphisms were associated with AD risk. Methods. AD cases (n = 278) were recruited from Department of Neurology at three teaching hospitals in Taiwan between 2007 and 2010. Controls (n = 422) were recruited from the elderly health check-up and volunteers in the hospital during the same time period. Four common (allele frequency > 5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to examine the association between sequence variants of CLU and AD. We also assessed how ApoE ε4 status, gender, and hypertension modify the association between CLU polymorphisms and AD risk.