Abstract:

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.

Key words: Cerebral small vessel disease, Micro bleeds, MTHFR