1Chinese PLA Medical School, Beijing, China.
2Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China.
J Neurosurg. 2024 Apr 5;141(4):936-944. doi: 10.3171/2024.1.JNS232121. Print 2024 Oct 1.
This study aimed to investigate whether high homocysteine (Hcy) levels associated with the MTHFR gene influence the formation of the collateral vascular network in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis (EDAS) by influencing the number of endothelial progenitor cells (EPCs) in peripheral blood.
A total of 118 Chinese patients with bilateral primary MMD were prospectively included. Blood samples were collected from the anterior cubital vein before surgery, and MTHFR rs9651118 was genotyped using high-throughput mass spectrometry to determine the genotype of the test specimen. Serum Hcy and EPC levels were measured, the latter with flow cytometry. Digital subtraction angiography was performed 6 months after EDAS, and the formation of collateral circulation was evaluated using the Matsushima grade system. The correlations between MTHFR rs9651118 genotype, Hcy and EPC levels, and Matsushima grade were compared.
Among the 118 patients, 53 had the TT genotype (wild type) of MTHFR rs9651118, 33 TC genotype (heterozygous mutation), and 32 CC genotype (homozygous mutation). The mean ± SD Hcy level was 13.4 ± 9.5 μmol/L in TT patients, 9.8 ± 3.2 μmol/L in TC patients, and 8.9 ± 2.9 μmol/L in CC patients (p < 0.001). The level of EPCs in the venous blood of TT patients was 0.039% ± 0.016%, that of TC patients 0.088% ± 0.061%, and that of CC patients 0.103% ± 0.062% (p < 0.001). When the rs9651118 gene locus was mutated, Matsushima grade was better (p < 0.001) but there was no difference between heterozygous and homozygous mutations.
The results suggest that the MTHFR rs9651118 polymorphism is a good biomarker for collateral vascular network formation after EDAS in MMD patients.
本研究旨在探讨高同型半胱氨酸（Hcy）水平与 MTHFR 基因是否通过影响外周血内皮祖细胞（EPC）的数量，影响脑底异常血管网病（MMD）患者颅内外血管融通术（EDAS）后侧支血管网络的形成。
前瞻性纳入 118 例双侧原发性 MMD 中国患者。手术前从前臂肘静脉采集血样，并使用高通量质谱法对 MTHFR rs9651118 进行基因分型，以确定试验标本的基因型。使用流式细胞术测量血清 Hcy 和 EPC 水平。EDAS 后 6 个月进行数字减影血管造影，使用 Matsushima 分级系统评估侧支循环形成情况。比较 MTHFR rs9651118 基因型、Hcy 和 EPC 水平与 Matsushima 分级之间的相关性。
在 118 例患者中，53 例为 MTHFR rs9651118 的 TT 基因型（野生型），33 例为 TC 基因型（杂合突变型），32 例为 CC 基因型（纯合突变型）。TT 患者的平均 Hcy 水平为 13.4 ± 9.5 μmol/L，TC 患者为 9.8 ± 3.2 μmol/L，CC 患者为 8.9 ± 2.9 μmol/L（p < 0.001）。TT 患者静脉血 EPC 水平为 0.039% ± 0.016%，TC 患者为 0.088% ± 0.061%，CC 患者为 0.103% ± 0.062%（p < 0.001）。当 rs9651118 基因座发生突变时，Matsushima 分级较好（p < 0.001），但杂合突变和纯合突变之间无差异。
研究结果表明，MTHFR rs9651118 多态性是 MMD 患者 EDAS 后侧支血管网络形成的良好生物标志物。
