Immune Response & Vascular Disease Unit, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
Dumfries & Galloway Royal Infirmary, Cargenbridge, Dumfries, DG2 8RX, Scotland, UK.
J Thromb Thrombolysis. 2022 Aug;54(2):330-338. doi: 10.1007/s11239-022-02678-6. Epub 2022 Aug 2.
To compare age at 1st ischaemic stroke (IS) in a cohort of juvenile (< 46 years of age) IS patients evaluated for the rs1801133 polymorphism (C → T677) of the methylene tetrahydrofolate reductase (MTHFR) gene; to identify predictors of age at IS and of type of cerebral vessel involvement, small vessel disease (SVD) vs large vessel disease (LVD) responsible for the IS; to evaluate possible associations between other clinical and laboratory variables. Retrospective cohort study on 82 MTHFR TT, 54 MTHFR TC and 34 MTHFR CC participants; data regarding age, sex, age at IS, history of dyslipidaemia, hypertension, smoking, migraine and homocysteine (HC) as well as neuroimaging were collected. Age at IS was lower in MTHFR TT than MTHFR TC and CC (35 ± 4 vs 38 ± 0 vs 40 ± 3 years, respectively, p = 0.002); plasma HC (median, interquartile range) was higher in MTHFR TT than in the other groups [16.7 (11.8, 28.6) vs 11.4 (8.2, 16.1) vs 9.8 (7.9, 1.3) respectively, p < 0.0001)] and was higher in SVD than LVD [17.4 (12.4, 32.5) vs 11.4 (8.8, 16.4) p < 0.0001]. MTHFR TT independently predicted age at IS (p = 0.0008) alongside smoking both as a categorical (p = 0.003) or continuous variable (p = 0.02), whereas HC independently predicted SVD as categorical (p = 0.01) and continuous variable (p < 0.0001). Smoking positively predicted plasma HC (p = 0.005) and negatively the activated partial thromboplastin ratio (aPTTr) (p = 0.02). Juvenile IS carriers of the MTHFR TT genotype develop their 1st occlusion on average 5 years earlier compared to the CC genotype; smoking contributes to this prematurity adversely affecting plasma HC and coagulation whereas plasma HC predicts IS secondary to SVD. Public health campaigns against smoking should highlight the prematurity of IS in the juvenile population.
比较接受 rs1801133 多态性（C→T677）的亚甲基四氢叶酸还原酶（MTHFR）基因甲基化青少年（<46 岁）缺血性中风（IS）患者队列中的首次 IS 发病年龄；确定 IS 发病年龄的预测因素以及负责 IS 的小血管疾病（SVD）与大血管疾病（LVD）的预测因素；评估其他临床和实验室变量之间的可能关联。对 82 名 MTHFR TT、54 名 MTHFR TC 和 34 名 MTHFR CC 参与者进行回顾性队列研究；收集了年龄、性别、IS 发病年龄、血脂异常、高血压、吸烟、偏头痛和同型半胱氨酸（HC）病史以及神经影像学数据。MTHFR TT 患者的 IS 发病年龄低于 MTHFR TC 和 CC（35±4 岁比 38±0 岁比 40±3 岁，p=0.002）；MTHFR TT 患者的血浆 HC 中位数（四分位数范围）高于其他组[16.7（11.8，28.6）比 11.4（8.2，16.1）比 9.8（7.9，1.3），p<0.0001]，SVD 高于 LVD[17.4（12.4，32.5）比 11.4（8.8，16.4），p<0.0001]。MTHFR TT 独立预测 IS 发病年龄（p=0.0008），与吸烟一起预测（无论是分类变量还是连续变量）（p=0.003 和 p=0.02），而 HC 独立预测 SVD 为分类变量（p=0.01）和连续变量（p<0.0001）。吸烟与血浆 HC 呈正相关（p=0.005），与活化部分凝血活酶时间比值（aPTTr）呈负相关（p=0.02）。与 CC 基因型相比，MTHFR TT 基因型的青少年 IS 携带者平均提前 5 年发生首次闭塞；吸烟会导致这种早熟，对血浆 HC 和凝血产生不利影响，而血浆 HC 可预测 SVD 引起的 IS。针对吸烟的公共卫生运动应强调青少年人群中 IS 的过早发生。
