MTHFR基因C677T位点、高同型半胱氨酸血症及其与传统危险因素在中国缺血性脑卒中患者早期神经功能恶化中的相互作用

MTHFR C677T, hyperhomocysteinemia, and their interactions with traditional risk factors in early neurological deterioration in Chinese patients with ischemic stroke.

作者信息

Zhou Qiang, Xu Zhiyao, Duan Yuanyuan, Tang Hui, Zhang Haitao, Liu Hua

机构信息

Department of Neurology, the Affiliated Hospital of Southwest Jiaotong University & The Third People's Hospital of Chengdu, Chengdu, Sichuan 610031, PR China.

Department of Neurology, the People's Hospital of Mianyang, Mianyang, Sichuan 621000, PR China.

出版信息

Heliyon. 2024 May 9;10(10):e31003. doi: 10.1016/j.heliyon.2024.e31003. eCollection 2024 May 30.

DOI:10.1016/j.heliyon.2024.e31003

PMID:38784530

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11112322/

Abstract

OBJECTIVE

This study aimed to investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) and any possible interactions between specific MTHFR alleles and traditional risk factors among a Han Chinese cohort.

METHODS

434 AIS patients were consecutively recruited between January 2017 and June 2019, including 129 END and 305 non-END cases. A candidate gene association study design was used to analyze the association between MTHFR gene polymorphism and END risk. The polymerase chain reaction-restriction fragment length polymorphism (RFLP) method was employed to genotype the MTHFR C677T polymorphism. The interactional analyses were performed using the multifactor dimensionality reduction test.

RESULTS

Hyperglycemia (odds ratio [OR]: 2.410, 95 % confidence interval [CI]: 1.436-4.046, p = 0.001), neurological function impairment (NIHSS score >5) (OR: 2.158, 95%CI: 1.337-3.484, = 0.002) on admission, and hyperhomocysteinemia (HHcy) (OR: 2.570, 95%CI: 1.229-5.376, = 0.012) were independently associated with END. The TT genotype (OR: 1.710, 95%CI: 1.021-2.863, p = 0.043) and T allele (OR: 1.710, 95%CI: 1.021-2.863, p = 0.043) of this C677T polymorphism were associated with susceptibility to END, and the TT genotype was more common in the subjects with HHcy (OR: 2.525, 95%CI: 1.111-5.739, P = 0.023). In addition, we also found interactions for END risk between the C677T polymorphism and traditional risk factors for END, including: hyperglycemia on admission, drinking, and moderate to severe neurological deficits (OR 1.237, 95 % CI 0.227-6.734), although the results were not statistically significant (p = 0.806).

CONCLUSIONS

Our results show a possible association between MTHFR C677T polymorphism and gene-environment interactions with END susceptibility in a Han Chinese cohort.

摘要

目的

本研究旨在探讨急性缺血性脑卒中（AIS）患者亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性与早期神经功能恶化（END）之间的关系，以及在汉族人群队列中特定MTHFR等位基因与传统危险因素之间的任何可能相互作用。

方法

2017年1月至2019年6月连续纳入434例AIS患者，包括129例END患者和305例非END患者。采用候选基因关联研究设计分析MTHFR基因多态性与END风险的关联。采用聚合酶链反应-限制性片段长度多态性（RFLP）方法对MTHFR C677T基因多态性进行基因分型。使用多因素降维检验进行相互作用分析。

结果

入院时高血糖（比值比[OR]：2.410，95%置信区间[CI]：1.436-4.046，p = 0.001）、神经功能损害（美国国立卫生研究院卒中量表[NIHSS]评分>5）（OR：2.158，95%CI：1.337-3.484，p = 0.002）和高同型半胱氨酸血症（HHcy）（OR：2.570，95%CI：1.229-5.376，p = 0.012）与END独立相关。该C677T基因多态性的TT基因型（OR：1.710，95%CI：1.021-2.863，p = 0.043）和T等位基因（OR：1.710，95%CI：1.021-2.863，p = 0.043）与END易感性相关，且TT基因型在HHcy患者中更常见（OR：2.525，95%CI：1.111-5.739，P = 0.023）。此外，我们还发现C677T基因多态性与END的传统危险因素之间存在END风险的相互作用，包括：入院时高血糖、饮酒和中度至重度神经功能缺损（OR 1.237，95%CI 0.227-6.734），尽管结果无统计学意义（p = 0.806）。