停經年齡、脂質代謝相關基因型、與晚發性阿茲海默病風險之關聯研究

Association between age of menopause, genetic polymorphisms of lipid metabolism-related genes, and the risk of late-onset Alzheimer’s disease (LOAD)

方瑞雯(Jui-Wen Fang)

指導教授 ： 程蘊菁

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.03412

摘要

背景：已知女性停經狀態會影響動情素對晚發性阿茲海默病的保護作用。脂質代謝對於阿茲海默病的病理變化影響極大，然而過去並無研究探討脂質代謝相關基因如何影響停經年齡與晚發性阿茲海默病風險間關連性。
方法：本研究為以醫院為本所進行的病例對照研究。研究對象包含從民國九十六年十一月至民國九十九年七月來自北台灣三家教學醫院的晚發性阿茲海默病女性患者(n=93)。對照組則是同一時期召集到的健檢民眾及醫院志工 (n=196)。本研究使用羅吉斯迴歸分析法估計停經年齡與晚發性阿茲海默病風險之關連性，並以脂質代謝相關基因（ApoE e4，SAR1B，CLU）進行分層分析及交互作用之探討。
結果：停經年齡與晚發性阿茲海默病風險間的關連性有統計上的顯著（相對於停經年齡大於五十歲者，停經年齡小於等於五十歲者的勝算比為2.44，百分之九十五信賴區間介於1.05-5.70）。此顯著關連性只出現於帶有ApoE e4的分群中（勝算比為14.99，百分之九十五信賴區間介於2.27-99.02），而不帶有ApoE e4的分群則不顯著。此外，ApoE e4與CLU （rs11136000）基因多型性對於停經年齡與晚發性阿茲海默病風險間關連性有顯著的交互作用。
結論：停經年齡與晚發性阿茲海默病風險間顯著相關。脂質代謝相關基因（ApoE e4與CLU）之基因型與停經年齡有顯著的交互作用。

關鍵字

停經年齡 ； 脂質代謝相關基因型 ； 晚發性阿茲海默病

並列摘要

Background. Menopausal status affects the protective effect of estrogen on the risk of late-onset Alzheimer’s disease (LOAD). Lipid metabolism has known to play a role on AD pathogenesis; however, no studies have explored how genetic polymorphisms of lipid metabolism related genes modify the association between age of menopause and the risk of LOAD.
Methods. This is a hospital-based case-control study. LOAD patients (n=93) were recruited from three hospitals in northern Taiwan from November 2007 to July 2010. Controls were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Logistic regression models were used to evaluate the association between age of menopause and the risk of LOAD. Stratification analyses were performed by genotypes of lipid metabolism related genes (ApoE e4, SAR1B, CLU).
Results. Age of menopause was significantly associated with the risk of LOAD [<=50 vs.>50 y/o, adjusted odds ratio (AOR) = 2.44, 95% confidence interval (CI) = 1.05-5.70]. This association remained significant among ApoE e4 carriers, but not non-carriers (AOR=14.99, 95% CI=2.27-99.02). ApoE e4 status and CLU (rs11136000) polymorphisms significantly interacted with age of menopause on the risk of LOAD (p=0.01 and 0.04, respectively).
Conclusions. Age of menopause was significantly associated with the risk of LOAD. Genotypes of lipid metabolism related genes (ApoE e4 and CLU) significantly modified this association.

並列關鍵字

age of menopause ； lipid metabolism-related genes

參考文獻

Alzheimer's association (2011). 2011 Alzheimer' s Disease Facts and Figures.

Baldereschi, M., A. Di Carlo, et al. (1998). "Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging." Neurology 50(4): 996-1002.

Chapman, J., J. Estupinan, et al. (1996). "A simple and efficient method for apolipoprotein E genotype determination." Neurology 46(5): 1484-1485.

Chen, H. K., Z. S. Ji, et al. (2011). "Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease." J Biol Chem 286(7): 5215-5221.

Chien, I. C., Y. C. Lin, et al. (2008). "Treated prevalence and incidence of dementia among National Health Insurance enrollees in Taiwan, 1996-2003." J Geriatr Psychiatry Neurol 21(2): 142-148.