Immune Response & Vascular Disease Unit, CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal.
Dumfries & Galloway Royal Infirmary, Dumfries, UK.
Blood Coagul Fibrinolysis. 2021 Sep 1;32(6):382-386. doi: 10.1097/MBC.0000000000001049.
The aim of the study was to compare age at first venous thromboembolism (VTE), plasma homocysteine and activated partial thromboplastin time ratio (aPTTr) amongst unprovoked VTE patients with the methylentetrahydrofolate reductase (MTHFR) C667T genotypes, and to identify predictors of age at first VTE, of plasma homocysteine and of the aPTTr; to evaluate whether heterozygous or homozygous prothrombin (PT) G20210A mutation lowered the age at first VTE when associated with MTHFR TT. Retrospective cohort study on 259 MTHFR TT, 76 MTHFR TC and 64 MTHFR CC participants with unprovoked VTE; each participant contributed age, sex, age at VTE, history of dyslipidaemia, hypertension, smoking, homocysteine (measured by enzyme immunoassay) and aPTTr (measured by standard coagulation assay). Age at first VTE was lower in MTHFR TT than MTHFR TC and CC (41 ± 14 vs. 50 ± 16 vs. 51 ± 12 years, respectively, P < 0.0001); plasma homocysteine was higher in MTHFR TT than in the other groups (22 ± 21 vs. 12 ± 11.6 vs. 10 ± 3.3 μmol/l, respectively, P = 0.0005) whilst aPTTr was not different. MTHFR TT independently predicted age at first VTE (P = 0.001), plasma homocysteine (P < 0.0001) alongside sex (P = 0.0007), age and smoking (P = 0.03 for both). Compound MTHFR TT with PT GA or AA had no lowering effect on age at first VTE compared with MTHFR TT alone (41 ± 13 vs. 41 ± 14 years). Plasma homocysteine inversely related to aPTTr in the MTHFR TT group (P = 0.003). MTHFR TT anticipates age at first VTE by an average of 10 years compared with MTHFR TC and CC genotypes.
研究目的在于比较原发性静脉血栓栓塞症（VTE）患者中，亚甲基四氢叶酸还原酶（MTHFR）C667T 基因型与首次 VTE 年龄、血浆同型半胱氨酸和活化部分凝血活酶时间比值（aPTTr）之间的关系，并确定首次 VTE 年龄、血浆同型半胱氨酸和 aPTTr 的预测因素；评估杂合或纯合凝血酶原（PT）G20210A 突变与 MTHFR TT 相关时是否会降低首次 VTE 年龄。对 259 例 MTHFR TT、76 例 MTHFR TC 和 64 例 MTHFR CC 原发性 VTE 患者进行回顾性队列研究；每位患者提供年龄、性别、VTE 年龄、血脂异常史、高血压史、吸烟史、同型半胱氨酸（通过酶免疫分析法测定）和 aPTTr（通过标准凝血测定法测定）。MTHFR TT 组的首次 VTE 年龄低于 MTHFR TC 和 CC 组（分别为 41±14 岁、50±16 岁和 51±12 岁，P<0.0001）；MTHFR TT 组的血浆同型半胱氨酸高于其他两组（分别为 22±21 岁、12±11.6 岁和 10±3.3μmol/L，P=0.0005），而 aPTTr 无差异。MTHFR TT 独立预测首次 VTE 年龄（P=0.001）、血浆同型半胱氨酸（P<0.0001）以及性别（P=0.0007）、年龄和吸烟（均 P=0.03）。与 MTHFR TT 单独相比，MTHFR TT 与 PT GA 或 AA 复合不降低首次 VTE 年龄（分别为 41±13 岁和 41±14 岁）。MTHFR TT 组血浆同型半胱氨酸与 aPTTr 呈负相关（P=0.003）。与 MTHFR TC 和 CC 基因型相比，MTHFR TT 平均提前 10 年预测首次 VTE 年龄。
