目的

分析西藏地区藏族人群亚甲基四氢叶酸还原酶（MTHFR）多态性及其与脑微出血的相关性。

方法

收集2020 年1 月到2022 年12 月西藏自治区人民医院收治的藏族人群脑小血管病患者150 例（其中脑微出血患者69 例）和性别、年龄与之匹配的健康对照者50 例。所有患者记录头颅MRI 检查结果。应用Logistic 回归分析脑微出血的危险因素，按脑微出血的部位分为脑叶微出血组和深部/幕下脑微出血组，采用单因素分析方法分析2组间流行病学指标和MTHFR C677T 位点多态性分布的差异，根据脑微出血解剖评估量表（MARS）评分将69 例脑微出血患者分为轻度、中度和重度组，计算脑微出血个数。采用χ² 检验分析MTHFR C667T 位点多态性在不同程度脑微出血患者中的分布差异。

结果

Logistic 回归分析发现同型半胱氨酸（HCY）（OR=0.256，P=0.018）和尿酸（OR=4.460，P=0.021）是脑小血管病患者脑微出血的独立危险因素。脑叶微出血组患者28 例（40.6%），脑深部/幕下微出血患者41 例（59.4%），脑叶微出血组患者年龄和脑微出血个数均大于脑深部/幕下微出血组［（68.51±10.13）岁 vs（61.25±8.13）岁；6（1，16）个 vs 4（1，13）个］，差异均具有统计学意义（t=2.637，P=0.013；Z=-2.347，P=0.023），而HCY 与MTHFR C667T 位点多态性分布2组间差异无统计学意义（P＞0.05）。根据MARS 评分，轻度微出血患者22 例，中度微出血患者28 例，重度微出血患者19 例，HCY 随着微出血程度的加重而逐渐升高［（15.81±6.33）μmol/L vs（17.08±6.97）μmol/L vs（19.40±7.01）μmol/L］，差异具有统计学意义（F=4.576，P=0.013），其中重度微出血患者TT 型的比例较高（26.3%），3组差异有统计学意义（χ²=17.692，P=0.007），而与健康对照组相比，脑微出血组患者CC 比例较低（47.8% vs 60.0%），TT 的比例较高（10.2% vs 4.0%），但二者差异无统计学意义（P＞0.05）。

结论

西藏地区携带MTHFR C677T 纯合突变TT 型患者的总体比例不高，但这部分患者产生的高HCY 血症引起脑微出血的风险较高，应尽早予以识别和干预。

Objective To analyze the correlation between methylenetetrahydrofolate reductase （MTHFR） polymorphism and cerebral microbleeds （CMB） in Tibetan population in Tibet.

Methods

From January 2020 to December 2022， 150 Tibetan patients with small cerebrovascular disease （including 69 with CMB） and 50 healthy controls， matched by gender and age， were collected from the People's Hospital of Tibet Autonomous Region. All patients underwent cranial MRI. Logistic regression was employed to identify the risk factors for CMB. The patients were divided into lobar and deep/infratentorial cerebral microbleeds group， and t-tests， Mann-Whitney U-tests， or χ² tests were used to analyze the epidemiologic measurements and MTHFR C677T polymorphism between these groups.According to the microbleed anatomical rating scale （MARS）， cases were stratified into mild （22）， moderate（28）， and severe （19） groups， with CMB counts calculated accordingly. The number of CMB was calculated according to MARS. χ² tests were used to compare the distribution of MTHFR C667T gene polymorphism across CMB severity groups.

Results

Homocysteine （HCY） （OR=0.256， P=0.018） and uric acid （OR=4.460，P=0.021） were identified as independent risk factors for CMB compared with those without microbleeds.There were significant differences in age （68.51±10.13 vs 61.25±8.13； t=2.637， P=0.013） and number of CMB ［6（1， 16） vs 4（1， 13）； Z=-2.347， P=0.023］ between patients with different locations of CMB， while no significant differences were found in HCY and MTHFR C667T gene polymorphism distribution. In the severity-stratified analysis， HCY levels progressively increased with MARS severity， showing significant difference among 3 groups ［（15.81±6.33）μmol/L vs （17.08±6.97）μmol/L vs （19.40±7.01）μmol/L； F=4.576，P=0.013］. Patients with severe CMB had a higher proportion of TT genotype （26.3%）， with a significant difference among the three groups （χ²=17.692， P=0.007）. Compared with the healthy control， patients with CMB had a lower proportion of CC in MTHFR C677T （47.8% vs 60.0%） and a higher proportion of TT（10.2% vs 4.0%）， though this difference was not statistically significant （P＞0.05）.

Conclusion

Although the prevalence of the TT genotype in Tibetan patients with CMB is not high， the risk associated with hyperhomocysteinemia is relatively elevated， warranting prompt identification and management.