MTHFR基因多态性和补充叶酸对缺血性脑卒中二级预防1年结局的影响

Effects of MTHFR Gene Polymorphism and Folate Supplementation on One-Year Outcome of Secondary Prevention for Ischemic Stroke

目的:考察MTHFR C677T和A1298C基因以及补充叶酸对缺血性脑卒中复发和改善的影响。方法:收集联勤保障部队第九六〇医院、泰安市中心医院于2018年3月至2019年2月和2021年6月至2022年5月收治的初发缺血性脑卒中且美国国立卫生院卒中神经功能缺损评分量表(NIHSS)评分为6~19分的患者,治疗出院后实施常规二级预防的为非暴露组,在常规二级预防的基础上口服叶酸(1次0.4 mg,1日3次)的为暴露组。非暴露组和暴露组患者按NIHSS评分接近的原则配对,各117例,检测MTHFR rs677和rs1298基因型。用队列研究的方法考察MTHFR基因多态性和补充叶酸与1年内脑卒中复发、1年内NIHSS评分降低程度的相关性。结果:两组患者MTHFR各基因型分布均符合Hardy-Weinberg遗传平衡定律。Logistic分析表明,脑卒中患者1年内复发与初发时NIHSS评分较高相关(P=0.042,OR=3.193,95%CI=1.104~9.238),但与MTHFR基因多态性或二级预防期间补充叶酸无关。多元线性回归结果表明,脑卒中患者1年内NIHSS评分降低程度与同时携带MTHFR C677T和A1298C基因(P=0.040,95%CI=0.081~3.178)以及初发时合并高同型半胱氨酸血症(HHcy)(P=0.046,95%CI=0.021~4.059)有关,但与二级预防期间补充叶酸无关。结论:在实施常规二级预防条件下,缺血性脑卒中复发与初发时的严重程度有关,与MTHFR基因多态性无关;携带MTHFR C677T和A1298C以及HHcy不利于脑卒中后1年内的康复,与是否补充叶酸无关。

OBJECTIVE:To investigate the effects of MTHFR C677T and A1298C genes as well as folate supplementation on the recurrence and improvement of ischemic stroke.METHODS:Patients with primary ischemic stroke and National Institutes of Health Stroke Neurological Deficiency Scale(NIHSS)score from 6 to 19 points admitted to the 960th Hospital of Joint Logistics Support Force of PLA and Tai’an Central Hospital from Mar.2018 to Feb.2019 and Jun.2021 to May 2022 were collected,those patients who received conventional secondary prevention after treatment and discharged from hospital were set as non-exposed group,and those patients who received folate orally(0.4 mg for once,3 times a day)based on conventional secondary prevention were set as exposed group.Patients in the non-exposed group and exposed group were paired according to the principle of proximity of NIHSS scores,with 117 cases in each group,which were tested for MTHFR rs677 and rs1298 genotypes.A cohort study was carried out to inspect the correlation between MTHFR gene polymorphisms and folate supplementation with stroke recurrence within 1 year and the decline degree of NIHSS scores within 1 year.RESULTS:The distribution of each genotype of MTHFR in both groups was in accordance with the Hardy-Weinberg law of genetic equilibrium.Logistic analysis showed that recurrence within 1 year in stroke patients was associated with higher NIHSS scores at the first attack(P=0.042,OR=3.193,95%CI=1.104-9.238),while it was not associated with MTHFR gene polymorphisms and folate supplementation during secondary prevention.Results of multivariate linear regression showed that the decline degree of NIHSS scores within 1 year in stroke patients was associated with carrying both MTHFR C677T and A1298C genes(P=0.040,95%CI=0.081-3.178)and with the complication of hyperhomocysteinemia(HHcy)at the first attack(P=0.046,95%CI=0.021-4.059),while it was not associated with folate supplementation during secondary prevention.CONCLUSIONS:Under the condition of conventional secondary prevention implementation,ischemic stroke recurrence is associated with the severity at the first attack and independent of MTHFR gene polymorphisms.MTHFR C677T and A1298C as well as HHcy worked against ischemic stroke recovery within a year,yet is not associated with folate supplementation.