台灣人自發性阿滋海默症相關危險因子的研究
Genetic Risk Factors of Sporadic Alzheimers Disease in Taiwan
中文摘要
阿滋海默症(Alzheimer s disease，簡稱 AD)是失智症最重要的病因之一，隨著 台灣人口的老化，阿滋海默症病人數亦持續增加，構成阿滋海默症的病因眾多，
如家族史，性別，雌性激素等等。目前已有許多証據顯示，遺傳基因因子在阿滋 海默症的發生上扮演了一個重要的角色。本實驗以 82 位自發性及晚發性的阿滋 海默症病患和 110 個健康老人為樣本，針對目前已知在染色體上和阿滋海默症可 能有關的九組相關基因的 polymorphisms 或突變，以統計方法分析其中致病的相 關性。
實驗中這九組和阿滋海默症相關的基因分別是 apolipoprotein E 4 (ApoE-4)，
promoter of apolipoprotein E (ApoE，G-186T)，regulatory region of apolipoprotein E (ApoE，A-491T)，mutation of α2-macroglobulin (A2M G2998A)，five nucleotide deletion of α2-macroglobulin，bleomycin hydrolase (BH，A1450G)，presenilin-1 intronic polymorphism (PS-1，allele 1/2 )， 1- antichymotrypsin (ACT， A/T)，
low-density receptor-related protein (LRP，C766T)，我們利用 PCR-RFLP
(Polymerase chain reaction-restriction fragment length polymorphism)的方法分析此 九組相關基因的多型性變化。
結果顯示，在這九組相關基因的 polymorphisms 或突變中只有 ApoE4 會增加罹患 AD 的危險性，且這九組相關基因彼此之間沒有 gene-gene interaction，所以除了 ApoE4 外，其餘八組基因的已知 polymorphisms 或突變對台灣人而言並非造成 AD 的相關基因。台灣 AD 病人可能另有不同於這幾組基因 polymorphisms 或突 變的危險因子或不在這些基因上，而繼續找尋可能的相關突變或其它候選基因將 是未來研究的重點。
英文摘要
Alzheimer s disease (AD) is one of the most important cause of the Dementia. In Taiwan, with the people population s aging, AD s patients are also continue increasing. Many factors may be involved in the pathogenesis of AD, for example, family history, sex and estrogen, etc. Up to now, a variety of studies have shown that genetic factor plays an important role in AD. In this study, we collected a total of 192 samples including 82 sporadic late- onset AD patients, and 110 health elders controls as samples. Different statistic programs were used to analyze the possible interaction of 9 AD related genes. The 9 sets of AD related genes include
apolipoprotein E 4 (ApoE-4), promoter of apolipoprotein E (ApoE, G-186T), regulatory region of apolipoprotein E (ApoE, A-491T), mutation of α
2-macroglobulin (A2M G2998A), five nucleotide deletion of α2-macroglobulin, bleomycin hydrolase (BH, A1450G), presenilin-1 intronic polymorphism (PS-1, allele 1/2 ), 1- antichymotrypsin (ACT, A/T), low-density receptor-related protein (LRP, C766T). PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) was used to analyze the polymorphisms or mutations of these 9 sets of AD related genes.
The results showed that only ApoE 4 significantly increases the risk of AD using these 9 sets of related genes. However, besides ApoE4, other 8 sets of related genes polymorphisms or mutations are not the factors to cause AD in Taiwan.
Taken together, AD patients in Taiwan may have other different high risk factors.
Continue searching for other polymorphisms or mutations of AD related genes or other candidates may be helpful in understanding the mechanism of AD
pathogenesis.
