Immune Response & Vascular Disease Unit, Universidade NOVA de Lisboa, Lisboa, Portugal.
Dumfries & Galloway Royal Infirmary, Dumfries, UK.
Blood Coagul Fibrinolysis. 2024 Jun 1;35(4):180-186. doi: 10.1097/MBC.0000000000001299. Epub 2024 Mar 20.
The aim of this study was to evaluate the impact of methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C→T667 transition) on age at first idiopathic portal vein thrombosis (PVT) and to identify clinical and/or laboratory variables influencing age at first PVT, including plasma homocysteine and the prothrombin rs1799963 PT (G→A transition at position 20210) (PT) mutation. A retrospective cross-sectional cohort, including 15 MTHFR TT, 32 MTHFR TC and 22 MTHFR CC idiopathic PVT participants contributing demographics, age at PVT, plasma concentrations of homocysteine and of natural anticoagulants. MTHFR TT carriers presented with a lower age at PVT than heterozygous or wild-type genotypes (31 ± 8 vs. 48 ± 15 vs. 52 ± 13 years, P = 0.001) and were more likely to have a plasma HC concentration above the cut-off (73.3 vs. 32 vs. 50%, P = 0.04). MTHFR TT and protein C predicted age at PVT ( P < 0.0001 and P = 0.06); MTHFR TT predicted plasma homocysteine ( P = 0.05). In the MTHFR TT group, plasma homocysteine inversely related to protein C ( P = 0.03). Plasma homocysteine predicted the extent of PVT ( P = 0.03). Compound MTHFR TT + PT GA did not lower age at first PVT compared to MTHFR TT alone (35 ± 9 vs. 30 ± 8 years). MTHFR TT is associated with a 20-year earlier PVT presentation than heterozygous and wild-type MTHFR genotypes. The inverse relation between plasma homocysteine and protein C contributes to the prematurity of PVT in the MTHFR TT group, whereas plasma homocysteine contributes to the extent of PVT. The recent exclusion of MTHFR genotyping from the thrombophilia screen needs revisiting in this setting.
本研究旨在评估亚甲基四氢叶酸还原酶（MTHFR）rs1801133（C→T667 转换）对首次特发性门静脉血栓形成（PVT）年龄的影响，并确定影响首次 PVT 年龄的临床和/或实验室变量，包括血浆同型半胱氨酸和凝血酶原 rs1799963 PT（G→A 转换位于 20210 位）（PT）突变。本研究为回顾性横断面队列研究，纳入了 15 例 MTHFR TT、32 例 MTHFR TC 和 22 例 MTHFR CC 特发性 PVT 患者，这些患者提供了人口统计学数据、PVT 年龄、血浆同型半胱氨酸和天然抗凝剂浓度。与杂合或野生型基因型相比，MTHFR TT 携带者的 PVT 年龄更小（31±8 岁比 48±15 岁比 52±13 岁，P=0.001），并且更有可能出现高于临界值的血浆 HC 浓度（73.3%比 32%比 50%，P=0.04）。MTHFR TT 和蛋白 C 预测 PVT 年龄（P<0.0001 和 P=0.06）；MTHFR TT 预测血浆同型半胱氨酸（P=0.05）。在 MTHFR TT 组中，血浆同型半胱氨酸与蛋白 C 呈负相关（P=0.03）。血浆同型半胱氨酸预测 PVT 的程度（P=0.03）。与单独的 MTHFR TT 相比，复合 MTHFR TT+PT GA 并未降低首次 PVT 的年龄（35±9 岁比 30±8 岁）。与杂合和野生型 MTHFR 基因型相比，MTHFR TT 与 PVT 提前 20 年发生相关。血浆同型半胱氨酸与蛋白 C 之间的反比关系导致 MTHFR TT 组 PVT 的过早发生，而血浆同型半胱氨酸导致 PVT 的程度。最近在血栓形成倾向筛查中排除 MTHFR 基因分型需要在此背景下重新考虑。
