乙醛脫氫酶和乙醇脫氫酶1B多態性在酒精暴露下會增加中風的風險

ALDH and ADH1B polymorphism may increase the risk of stroke with alcohol exposure

林君襄(Chun-Hsiang Lin)

指導教授 ： 廖勇柏

共同指導教授 ： 陳哲宏(Che-Hong Chen)

中山醫學大學/健康管理學院/公共衛生學系/博士(2023年)

https://doi.org/10.6834/csmu202200266

摘要

流行病學研究已經確定了全世界腦中風的常見危險因素。其中一些因素包括高血壓、糖尿病、吸煙、過度飲酒和血脂異常。然而，重要的是要注意遺傳因素也可能導致中風的發生。我們納入了來自兩個資料庫的數據：(1) 國家健康保險研究數據庫 (NHIRD)，提供 1998 年至 2015 年的醫學數據；(2) 台灣人體生物資料庫，一個對研究人員開放並包含基本人口統計和基因型的國家健康資源，蒐羅 2008 年至 2015 年台灣居民（30 至 70 歲）的數據。我們將衛生福利資料科學中心（HWDC）的兩個數據庫通過個人身份證號碼鏈接起來，並獲取有關中風發生率的相關數據。

本論文有兩個主要部分。在第一部分中，我們旨在評估中風與酒精代謝基因：乙醇脫氫酶 1B (ADH1B, rs1229984) 和乙醛脫氫酶 2 (ALDH2, rs671) 基因的遺傳多態性與飲酒之間的關聯。我們發現 ADH1B rs1229984 TC+CC 基因型加上每周至少 150 毫升的酒精暴露可能會增加台灣成年人發生出血性中風的風險。在第二部分中，我們評估了缺血性中風與 rs12514417 多態性以及酒精代謝基因：乙醛脫氫酶 7A1 (ALDH7A1) 基因和飲酒之間的關係。研究表明，ALDH7A1 rs12514417 TG+GG 基因型加上每周至少 150 毫升的酒精暴露可能會增加台灣成年人缺血性中風的風險。我們建議對不同人群中的基因-環境相互作用進行大型研究，並使用動物模型或人類細胞進行功能評估，以探討這種潛在關聯背後的潛在機制。

關鍵字

乙醛脫氫酶 ； 乙醇脫氫酶 ； 酒精 ； 中風

並列摘要

doi:10.6834/csmu202200266 3

英文摘要
Epidemiological studies have led to the identification of common risk factors
for stroke worldwide. Among these factors are hypertension, diabetes, smoking,
excessive alcohol consumption and hyperlipidemia. It should be noted, however,
that genetic factors and the nutrition status may also contribute to the onset of
stroke. We combined the two data resources and linked through personal ID
numbers: (1) We obtained the disease data from The National Health Insurance
Research Database (NHIRD), with medical data available from 1998 to 2015 and
(2) The basic demographic and genetic information was from Taiwan Biobank, an
ongoing prospective study of >150,000 individuals aged 20–70 in Taiwan that is
open to researchers from 2008 to 2015.
The thesis consists of two major parts. In the first part, we aimed to evaluate
the association of genetic polymorphisms in the alcohol metabolizing genes
(Alcohol Dehydrogenase 1B (ADH1B, rs1229984) and Aldehyde Dehydrogenase 2
(ALDH2, rs671) genes) and both types of stroke based on alcohol consumption.
Genotype ADH1B rs1229984 TC+CC with concurrent alcohol exposure of at least
150 ml/week were found to increase the risk of hemorrhagic strokes in
Taiwanese adults. In the second part, we evaluated the association of ischemic
stroke with rs12514417 polymorphism and of the alcohol metabolizing genes,
aldehyde dehydrogenase 7A1 (ALDH7A1) gene and alcohol consumption. The
study suggested that the ALDH7A1 rs12514417 TG+GG genotype and alcohol
exposure of at least 150 ml/week may increase the risk of ischemic stroke in
Taiwanese adults. We suggested further study conducted in different ethnic
groups to see gene-environment interactions. In addition, consider to use animal
models or human cell lines to do functional assessment and try to find out the
underlying mechanisms behind this potential association.

並列關鍵字

ALDH ； ADH ； stroke ； alcohol

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