Abstract：
BACKGROUND: The impact of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation on the relationship between plasma homocysteine (Hcy) levels and stroke has been extensively studied and documented in previous study. However, it remains unclear whether the MTHFR C677T mutation can affect the response to Hcy lowering treatment in stroke patients with hyperhomocysteinemia (HHcy). Understanding the impact of genetic factors on treatment response can help optimize personalized treatment strategies for stroke patients with HHcy. We aimed to investigate the potential association between the MTHFR C677T gene polymorphisms and the effectiveness of Hcy lowering treatment using vitamin therapy in stroke patients with HHcy.
METHODS: The MTHFR C677T genotype polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism, and the distribution of three genotypes in the MTHFR C677T gene locus was compared. The treatment effects of Hcy lowering agents were compared among patients with different genotypes.
RESULTS: Among the 320 stroke patients enrolled in the study, 258 (80.6%) were diagnosed with HHcy. Of these, 162 patients (Effective Group) responded well to the clinical Hcy lowering treatment, while 96 patients (Invalid Group) failed to achieve sufficient response even after taking combination supplements of folic acid, Vitamin B6, and methylcobalamin for one month. Significant differences were observed in terms of age (p < 0.001), hypertension (p = 0.034), dyslipidemia (p = 0.022), hyperuricemia (p = 0.013) and genotype distribution of MTHFR C677T gene polymorphism (p < 0.001) between the Invalid group and the Effective group. The multivariate regression analysis revealed that the T allele (odd rations [OR], 1.327; 95% confidence interval [CI], 1.114-1.580; p = 0.0015) was independently associated with an insufficient Hcy lowering treatment effect. Additionally, the TT genotype was independently associated with insufficient response in both the codominant model (OR, 1.645; 95% CI, 1.093-2.476; p = 0.017) and the recessive model (TT versus CC + CT; OR, 1.529; 95% CI, 1.145-2.042; p = 0.004). However, no relationship was observed between CT + TT genotypes and poor treatment effect in the dominate model.
CONCLUSIONS: Our findings suggested that the TT genotype and T allele of MTHFR C677T polymorphism were independently associated with an insufficient Hcy lowering treatment effect in stroke patients with HHcy.
METHODS: The MTHFR C677T genotype polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism, and the distribution of three genotypes in the MTHFR C677T gene locus was compared. The treatment effects of Hcy lowering agents were compared among patients with different genotypes.
RESULTS: Among the 320 stroke patients enrolled in the study, 258 (80.6%) were diagnosed with HHcy. Of these, 162 patients (Effective Group) responded well to the clinical Hcy lowering treatment, while 96 patients (Invalid Group) failed to achieve sufficient response even after taking combination supplements of folic acid, Vitamin B6, and methylcobalamin for one month. Significant differences were observed in terms of age (p < 0.001), hypertension (p = 0.034), dyslipidemia (p = 0.022), hyperuricemia (p = 0.013) and genotype distribution of MTHFR C677T gene polymorphism (p < 0.001) between the Invalid group and the Effective group. The multivariate regression analysis revealed that the T allele (odd rations [OR], 1.327; 95% confidence interval [CI], 1.114-1.580; p = 0.0015) was independently associated with an insufficient Hcy lowering treatment effect. Additionally, the TT genotype was independently associated with insufficient response in both the codominant model (OR, 1.645; 95% CI, 1.093-2.476; p = 0.017) and the recessive model (TT versus CC + CT; OR, 1.529; 95% CI, 1.145-2.042; p = 0.004). However, no relationship was observed between CT + TT genotypes and poor treatment effect in the dominate model.
CONCLUSIONS: Our findings suggested that the TT genotype and T allele of MTHFR C677T polymorphism were independently associated with an insufficient Hcy lowering treatment effect in stroke patients with HHcy.
摘要：
背景：亚甲基四氢叶酸还原酶（MTHFR）C677T突变对血浆同型半胱氨酸（Hcy）水平与卒中之间关系的影响已得到广泛研究和记录。然而,目前尚不清楚MTHFRC677T突变是否会影响合并高同型半胱氨酸血症(HHcy)的卒中患者对降低Hcy治疗的反应.了解遗传因素对治疗反应的影响有助于优化脑卒中患者HHcy的个性化治疗策略。我们的目的是研究MTHFRC677T基因多态性与使用维生素治疗的脑卒中患者降低Hcy治疗效果之间的潜在关联。
方法：使用聚合酶链反应-限制性片段长度多态性鉴定MTHFRC677T基因型多态性，并比较了三种基因型在MTHFRC677T基因位点的分布。比较不同基因型患者使用降低Hcy药物的治疗效果。
结果：在参与研究的320名中风患者中，258例(80.6%)被诊断为HHcy。其中,162例患者（有效组）对临床降低Hcy治疗反应良好，而96名患者（无效组）即使在服用叶酸的联合补充剂后也未能达到足够的反应，维生素B6和甲钴胺一个月。在年龄方面观察到显著差异(p<0.001)，高血压（p=0.034），血脂异常（p=0.022），无效组和有效组之间的高尿酸血症（p=0.013）和MTHFRC677T基因多态性的基因型分布（p<0.001）。多元回归分析显示，T等位基因(奇数比[OR]，1.327；95%置信区间[CI]，1.114-1.580；p=0.0015）与Hcy降低治疗效果不足独立相关。此外,在两个共显性模型中，TT基因型与反应不足独立相关(OR，1.645；95%CI，1.093-2.476；p=0.017）和隐性模型（TT与CC+CT；OR，1.529；95%CI，1.145-2.042；p=0.004）。然而,在优势模型中，未观察到CT+TT基因型与治疗效果差之间的关系。
结论：我们的发现表明，MTHFRC677T多态性的TT基因型和T等位基因与卒中患者HHcy降低治疗效果不足独立相关。
方法：使用聚合酶链反应-限制性片段长度多态性鉴定MTHFRC677T基因型多态性，并比较了三种基因型在MTHFRC677T基因位点的分布。比较不同基因型患者使用降低Hcy药物的治疗效果。
结果：在参与研究的320名中风患者中，258例(80.6%)被诊断为HHcy。其中,162例患者（有效组）对临床降低Hcy治疗反应良好，而96名患者（无效组）即使在服用叶酸的联合补充剂后也未能达到足够的反应，维生素B6和甲钴胺一个月。在年龄方面观察到显著差异(p<0.001)，高血压（p=0.034），血脂异常（p=0.022），无效组和有效组之间的高尿酸血症（p=0.013）和MTHFRC677T基因多态性的基因型分布（p<0.001）。多元回归分析显示，T等位基因(奇数比[OR]，1.327；95%置信区间[CI]，1.114-1.580；p=0.0015）与Hcy降低治疗效果不足独立相关。此外,在两个共显性模型中，TT基因型与反应不足独立相关(OR，1.645；95%CI，1.093-2.476；p=0.017）和隐性模型（TT与CC+CT；OR，1.529；95%CI，1.145-2.042；p=0.004）。然而,在优势模型中，未观察到CT+TT基因型与治疗效果差之间的关系。
结论：我们的发现表明，MTHFRC677T多态性的TT基因型和T等位基因与卒中患者HHcy降低治疗效果不足独立相关。
