CYP2C9基因單核苷酸多型性與缺血性中風的相關性研究—以臺灣人體生物資料庫為例

Relationship between ischemic stroke and CYP2C9 polymorphisms in Taiwan Biobank subjects

彭瑞炆(Jui-Wen Peng)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/博士(2022年)

https://doi.org/10.6834/csmu202200127

摘要

第一節 CYP2C9基因多型性、心房顫動與缺血性中風
研究目的：缺血性中風是全球的健康問題，約占所有中風的85%。根據CYP2C9的rs2860905變異，本研究評估了臺灣人體生物資料庫之參與者中，其缺血性中風與心房顫動的相關性。
研究材料與方法：資料來源為臺灣人體生物資料庫 (Taiwan Biobank, TWB)及全民健康保險資料庫 (National Health Insurance Research Database, NHIRD)，取自2008年至2015年期間，共招募17,726位成年人。使用邏輯斯回歸進行分析並估算出缺血性中風之勝算比 (Odds ratio, OR)及95%信賴區間 (95% confidence intervals, CI)。
研究結果：在17,726的參與者中，有906位患有缺血性中風。整體分析中，結果發現心房顫動與缺血性中風的風險增加相關，其OR 值及95%信賴區間分別為3.70以及2.21-6.20，而rs2860905則不相關。也就是說，與GG基因型相比，GA /AA基因型得到缺血性中風的機會OR為1.00 (95％CI，0.82-1.22)。根據基因型分層分析，僅在GG基因型患者中，心房顫動才是重要的危險因子 (OR = 4.68；95％CI=2.70-8.09)。
結論與建議：CYP2C9 rs2860905 GG基因型在臺灣成年人中，缺血性中風與心房顫動之間的關係相對於GA / AA基因型的成年人較強。

第二節 CYP2C9基因多型性、性別與缺血性中風
研究目的：中風是一種由多種危險因子所引起的複雜健康狀況。我們透過TWB參與者之資料調查了CYP2C9 rs4918758 多型性和性別是否對缺血性中風之風險具有獨立且交互作用之相關性。
研究材料與方法：我們分析了9,197 名女性和 8,625 名男性的 TWB 資料。 2008 年至 2015 年間收集的數據與國家健康保險數據庫 (NHIRD) 中的醫療記錄串聯。透過多重邏輯回歸分析，我們估計了缺血性中風的勝算比 (Odds ratio, OR) 和 95% 信賴區間 (CI)。
研究結果：我們發現 441 名女性和 468 名男性患有缺血性中風。帶有rs4918758 TC/CC多型性與帶有 TT多型性之間的缺血性中風之風險沒有顯著差異 [OR (95% CI) = 1.04 (0.90-1.21)]。與女性相比，男性缺血性中風的 OR 為 1.03 (95% CI = 0.87-1.22)。根據本研究的進一步分析，發現性別與rs4918758 基因多型性具有交互作用 (交互作用的 p = 0.0019)。按性別進行分層分析後，具有 TC/CC 基因型的男性表現出顯著的 OR，但女性沒有 [OR (95% CI) = 1.32 (1.07-16.33) vs 0.83 (0.68-1.00)]；按rs4918758 基因多型性進行分層分析後顯示，與女性相比，具有 TT 和 TC/CC 基因型的男性的 OR 分別為 0.59 (95% CI = 0.44-0.80)和 1.36 (95% CI = 1.10-1.68)。
結論與建議：根據我們的研究，與女性相比，rs4918758 的 TT 基因型與臺灣男性缺血性中風之風險降低相關，而 TC/CC 基因型則與更高的缺血性中風之風險相關。

關鍵字

CYP2C9 ； 中風 ； 單核苷酸多型性 中風 ； 基因變異 ； 性別 ； 缺血性心臟 ； 性別

並列摘要

第一節 CYP2C9基因多型性、心房顫動與缺血性中風
Objective: Ischemic stroke remains a global health problem, accounting for approximately 85% of all stroke. We assessed the relationship between ischemic stroke and atrial fibrillation among Taiwan biobank participants based on the rs2860905 variant of the cytochrome P450 Family 2 Subfamily C Member 9 (CYP2C9) gene.
Material and Methods: Using logistic regression analysis, we estimated the odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke among 17,726 biobank adults recruited from 2008 through 2015.
Results: Of the eligible individuals (n = 17,726), 906 were identified with ischemic stroke. In our overall analysis, atrial fibrillation was associated with an increased risk of ischemic stroke (OR=3.70; 95% CI, 2.21-6.20), whereas the rs2860905 variant was not. That is, the OR for ischemic stroke among those with GA/AA genotype was 1.00 (95% CI, 0.82-1.22) compared to those with GG genotype. Based on the genotype-stratified analysis, atrial fibrillation was found to be a significant risk factor only among those with GG genotype (OR=4.68; 95% CI, 2.70-8.09).
Conclusion: These results demonstrate that the relationship between ischemic stroke and atrial fibrillation is stronger among Taiwanese adults with CYP2C9 rs2860905 GG genotype relative to those with GA/AA genotype.

第二節 CYP2C9基因多型性、性別與缺血性中風
Objective: Stroke is a complex health condition caused by multiple risk factors. We investigated whether the Cytochrome P450 2C9 (CYP2C9) rs4918758 polymorphism and sex were independently and interactively associated with ischemic stroke risk among Taiwan Biobank (TWB) participants.
Material and Methods: We analyzed TWB data pertaining to 9197 female and 8625 male individuals. Data collected between 2008 and 2015 were linked to medical records in the National Health Insurance Database (NHIRD). Based on multiple logistic regression analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke.
Results: We found that 441 women and 468 men had ischemic stroke. There were no differences in the risk of ischemic stroke between individuals with the TC/CC genotype and those with the TT genotype [OR (95% CI) = 1.04 (0.90-1.21)]. When compared to women, men had an OR of 1.03 (95% CI = 0.87-1.22) for ischemic stroke. Based on further analysis, sex was found to interact with polymorphism rs4918758 (p for interaction = 0.0019). After categorizing by sex, men with TC/CC genotype showed significant ORs but not women [OR (95% CI) = 1.32 (1.07-16.33) vs 0.83 (0.68-1.00)]. Further stratification by genotype showed that in comparison with their female counterparts, men with the TT and TC/CC genotypes had ORs of 0.59 (95% CI = 0.44-0.80) and 1.36 (95% CI = 1.10-1.68), respectively.
Conclusion: According to our study, the TT genotype of rs4918758 was associated with a reduced risk of ischemic stroke in Taiwanese men when compared to women, whereas the TC/CC genotype was associated with a greater risk.

並列關鍵字

CYP2C9 ； stroke ； single nucleotide polymorphism stroke ； genetic variant ； sex ； ischemic heart ； gender

參考文獻

參考文獻

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