亚甲基四氢叶酸还原酶 C677T 基因型 TT 纯合子与早发性心肌梗死患者的心脏性死亡有独立的长期相关性。

Homozygosity of the TT methylenetetrahydrofolate reductase C677T genotype is an independent long-term predictor of cardiac death in patients with premature myocardial infarction.

机构信息

Second Department of Cardiology, National & Kapodistrian University of Athens School of Medicine, University General Hospital Attikon, Athens, Greece.

Department of Clinical Biochemistry, National & Kapodistrian University of Athens School of Medicine, University General Hospital Attikon, Athens, Greece.

出版信息

Curr Med Res Opin. 2021 Jul;37(7):1079-1084. doi: 10.1080/03007995.2021.1912720. Epub 2021 Apr 21.

DOI:10.1080/03007995.2021.1912720

PMID:33813997

Abstract

BACKGROUND

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is the main genetic modulator of homocysteine. Data suggest a potential association of homozygosity for the TT MTHFR genotype with premature myocardial infarction (MI). We explored whether TT homozygosity is associated with long-term prognosis in patients with premature ST-segment elevation MI (STEMI).

METHODS

A total of 265 consecutive patients who had survived their first STEMI ≤35 years of age were followed for a median of 8 years (5-12). Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. Serum lipids, homocysteine, folate levels were measured at baseline and all patients were also tested for the MTHFR C677T polymorphism.

RESULTS

During follow-up 14 patients died (cardiac death) [5.3%] while 84 (31.7%) met the secondary endpoints. In univariate Cox regression analysis TT homozygosity predicted the occurrence of cardiac death (Hazard ratio (HR): 4.071; 95% confidence interval (CI): 1.404-11.809, = .010) but not the occurrence of secondary endpoints (HR: 0.877; 95% CI: 0.479-1.605, = .669). TT homozygosity remained an independent predictor of cardiac death after adjustment for conventional risk factors (i.e., sex, diabetes mellitus, hypertension, family history of premature coronary artery disease [CAD]) [HR: 4.350; 95% CI: 1.472-12.856, = .008]. The association also remained after adjustment for left ventricular ejection fraction or the presence of significant CAD.

CONCLUSIONS

Homozygosity for the TT MTHFR is an independent long-term predictor of cardiac death in patients with premature STEMI.

摘要

背景

亚甲基四氢叶酸还原酶（MTHFR）C677T 多态性是同型半胱氨酸的主要遗传调节剂。有数据表明 TT MTHFR 基因型纯合子与早发性心肌梗死（MI）之间存在潜在的关联。我们探讨了 TT 纯合子是否与早发性 ST 段抬高型心肌梗死（STEMI）患者的长期预后相关。

方法

对 265 例首次 STEMI 年龄≤35 岁的连续患者进行了中位 8 年（5-12 年）的随访。主要终点是心脏性死亡，次要终点是因急性冠状动脉综合征、血运重建、心律失常事件或缺血性卒中住院。在基线时测量了血脂、同型半胱氨酸和叶酸水平，所有患者还检测了 MTHFR C677T 多态性。

结果

随访期间有 14 例患者（心脏性死亡）死亡（5.3%），84 例患者（31.7%）发生次要终点事件。在单变量 Cox 回归分析中，TT 纯合子预测了心脏性死亡的发生（危险比（HR）：4.071；95%置信区间（CI）：1.404-11.809， = .010），但不能预测次要终点事件的发生（HR：0.877；95% CI：0.479-1.605， = .669）。在调整传统危险因素（即性别、糖尿病、高血压、早发冠心病家族史）后，TT 纯合子仍然是心脏性死亡的独立预测因子（HR：4.350；95% CI：1.472-12.856， = .008）。在调整左心室射血分数或存在显著 CAD 后，该关联仍然存在。