探討吸菸與MTHFR(rs4846048)基因對神經退化性疾病的交互作用

The interaction of smoking and MTHFR(rs4846048) gene on the neurodegenerative disorder.

鍾季涵(Ji-Han Zhong)

指導教授 ： 廖勇柏

中山醫學大學/健康管理學院/公共衛生學系/碩士(2021年)

https://doi.org/10.6834/csmu202100161

摘要

隨著全球人口的高齡化，神經退化性疾病已是全世界所關注的重要公共衛生議題。外在的環境因素與內在的遺傳變異皆是影響疾病的重要關鍵，而本研究目的在於探討吸菸與MTHFR rs4846048基因型(AA型與AG+GG型)對神經退化性疾病的影響。
本研究是一篇橫斷面研究，使用了臺灣人體生物資料庫與全民健康保險研究資料庫的資料進行分析，共納入了17,914名參與者。在調整了年齡、性別、BMI、教育程度、飲酒、以及運動的情況下，利用邏輯斯迴歸將吸菸和rs4846048基因型進行分層分析與組合性分析。
本研究結果顯示，吸菸與rs4846048基因型對於神經退化性疾病有交互作用。在rs4846048基因型的分層分析中，AA型的人有14,470名，AG+GG型的人有3,444名，在AG+GG型的參與者中，吸菸會對得病風險造成顯著的影響，勝算比與95%信賴區間分別為4.12與1.31-12.96；在吸菸的分層分析中，不吸菸者有13,509名，吸菸者有4,405名，在不吸菸者中，AG+GG基因型會為得病風險帶來顯著的影響，勝算比與95%信賴區間分別為0.53與0.29-0.97；在rs4846048基因型與吸菸的組合性分析中，以AA型且不吸菸的參與者為參考組，對於AG+GG型且不吸菸的參與者，其得病風險具有統計學上的顯著意義，勝算比與95%信賴區間分別為0.53與0.29-0.97。在此，可看出吸菸的有害效果與AG+GG型的保護效果。
在具有rs4846048之AG+GG基因型的參與者中，吸菸者的得病風險將會比具有AG+GG型的不吸菸者來的高，此現象顯示了吸菸的危險效果。而在不吸菸的參與者中，AG+GG型的不吸菸者的得病風險將會比AA型的不吸菸者來的低，此現象顯示了AG+GG基因型的保護效果。

關鍵字

神經退化性疾病 ； 阿茲海默症 ； 帕金森氏症 ； 吸菸 ； MTHFR ； rs4846048

並列摘要

With the aging of the global population, neurodegenerative disorder has become an important public health concern of worldwide. Both external environmental factors and internal genetic variation are the important key to affecting diseases. The purpose of this study is to explore the effects of smoking and MTHFR rs4846048 genotype (AA genotype and AG+GG genotype) on neurodegenerative disorder.
This study is a cross-sectional study, using data from the Taiwan Biobank and the National Health Insurance Research Database for analysis. A total of 17,914 participants were included. After adjusting for gender, age, education level, drinking, exercise, and BMI, we use the logistic regression to do stratified analysis and combinatorial analysis of smoking and rs4846048 genotype.
The results of this study show that smoking and rs4846048 genotype have an interactive effect on neurodegenerative disorder. In the stratified analysis of rs4846048 genotypes, there are 14,470 people with AA genotype and 3,444 people with AG+GG genotype. Among the participants with AG+GG genotype, smoking has a significant impact on the risk of getting disease. The odds ratio and the 95% confidence interval are 4.12 and 1.31-12.96, respectively. In the stratified analysis of smoking, there are 13,509 non-smokers and 4,405 smokers. Among the non-smokers, AG+GG genotype has a significant impact on the risk of getting disease. The odds ratio and the 95% confidence interval are 0.53 and 0.29-0.97, respectively. In the combinatorial analysis of rs4846048 genotypes and smoking, the participants with AA genotype and no smoking, is used as the reference group. For the group of participants with AG+GG genotype and no smoking, the risk of getting disease is statistically significant. The odds ratio and 95% confidence interval are 0.53 and 0.29-0.97, respectively. In this regard, we can see the harmful effect of smoking and the protective effect of AG+GG genotype.
Among the participants with AG+GG genotype of rs4846048, the risk of getting the disease of smokers will be higher than the non-smokers with AG+GG genotype. The phenomenon shows the dangerous effect of smoking. Among the participants without smoking, the risk of getting disease of non-smokers with AG+GG genotype, will be lower than the non-smokers with AA genotype. The phenomenon shows that the protective effect of AG+GG genotype.

並列關鍵字

Neurodegenerative disorder ； Alzheimer's disease ； Parkinson's disease ； smoking ； MTHFR ； rs4846048

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