Sex-Specific Association between HO-1 (GT)n Promoter Polymorphism and Large-Artery Atherosclerosis Stroke.

IF 3 2区医学 Q2 PERIPHERAL VASCULAR DISEASE

Journal of atherosclerosis and thrombosis Pub Date : 2025-03-28 DOI:10.5551/jat.65595

Jintao Li, Junting Chen, Jia Wen, Kailin Cheng, Xiaoli Fu, Shuen Li, Zhu Shi

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引用次数: 0

Abstract

Aims: Oxidative stress is a central factor in the pathogenesis of atherosclerosis and potentially exhibits sexual dimorphism. The induction of heme oxygenase-1 (HO-1) serves as a crucial mechanism against reactive oxygen species toxicity in the vascular wall, and this induction is regulated by the promoter (GT)n repeat length. We aim to investigate whether or not HO-1 gene (GT)n polymorphism is associated with the occurrence of large-artery atherosclerotic (LAA) stroke.

Methods: We consecutively recruited stroke patients, with a control group comprising age- and sex-matched non-stroke individuals. HO-1 (GT)n genotypes were determined using DNA extracted from the peripheral leukocytes. HO-1 (GT)n polymorphism was classified as short [S, ≤ 24 (GT)n], medium [M, 25 ≤ (GT)n ＜31], or long [L, 31 ≤ (GT)n]. Clinical data were collected, and stroke patients were categorized into LAA and non-LAA groups according to the TOAST classification. A multivariable logistic regression analysis was conducted to evaluate the association between HO-1 (GT)n variants and LAA occurrence stratified by sex.

Results: There was no significant difference in the distribution of HO-1 (GT)n genotypes between the stroke and non-stroke populations. However, the proportion of S/S genotype was significantly lower in the LAA stroke patients than in the non-LAA stroke patients (7.08% vs. 21.78%, p＜0.001). A multivariable logistic regression analysis indicated that non-SS genotypes were associated with a significantly increased risk of LAA compared to the S/S genotype patients (odds ratio [OR] 3.35, 95% confidence interval [CI] 1.98-5.67, p＜0.001). After stratification by sex, the protective effect of the HO-1 (GT)n S/S genotype was highly significant in men (OR 5.50, 95% CI 2.67-11.34, p＜0.001), whereas the association was not significant in women (OR 1.60, 95% CI 0.75-3.34, p = 0.228).

Conclusion: Short (GT)n variants in HO-1 may confer significant protection against LAA stroke in men but not in women.

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HO-1 (GT)n启动子多态性与大动脉粥样硬化性卒中的性别特异性关联

目的：氧化应激是动脉粥样硬化发病的核心因素，并可能表现出性别二态性。血红素加氧酶-1 （HO-1）的诱导是对抗血管壁活性氧毒性的重要机制，这种诱导受启动子（GT）n重复长度的调节。我们的目的是研究HO-1基因（GT）n多态性是否与大动脉粥样硬化（LAA）卒中的发生有关。方法：我们连续招募脑卒中患者，对照组由年龄和性别匹配的非脑卒中个体组成。采用外周白细胞提取DNA测定HO-1 (GT)n基因型。HO-1 (GT)n多态性分为短态[S，≤24 (GT)n]、中态[M， 25≤(GT)n <31]和长态[L， 31≤(GT)n]。收集临床资料，根据TOAST分级将脑卒中患者分为LAA组和非LAA组。采用多变量logistic回归分析来评估按性别分层的HO-1 (GT)n变异与LAA发生之间的关系。结果：脑卒中人群与非脑卒中人群HO-1 (GT)n基因型分布无显著性差异。而LAA脑卒中患者中S/S基因型比例明显低于非LAA脑卒中患者（7.08% vs. 21.78%, p<0.001）。多变量logistic回归分析显示，与S/S基因型患者相比，非ss基因型患者发生LAA的风险显著增加（优势比[OR] 3.35, 95%可信区间[CI] 1.98 ~ 5.67, p<0.001）。按性别分层后，HO-1 （GT）和S/S基因型的保护作用在男性中非常显著（OR 5.50, 95% CI 2.67-11.34, p<0.001），而在女性中不显著（OR 1.60, 95% CI 0.75-3.34, p = 0.228）。结论：HO-1的短（GT）n变异可能对男性LAA卒中具有显著的保护作用，但对女性没有作用。

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