Associations of MTHFR gene polymorphism with lipid metabolism and risk of cerebral infarction in the Northwest Han Chinese population

Dong Guan; Yichun Ji; Xiaoyun Lu; Weiyi Feng; Wenbing Ma

doi:10.3389/fneur.2023.1152351

Associations of MTHFR gene polymorphism with lipid metabolism and risk of cerebral infarction in the Northwest Han Chinese population

Front Neurol. 2023 Mar 31:14:1152351. doi: 10.3389/fneur.2023.1152351. eCollection 2023.

Authors

Dong Guan¹, Yichun Ji², Xiaoyun Lu³, Weiyi Feng¹, Wenbing Ma^{1

3}

Affiliations

¹ Department of Pharmacology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
³ Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Abstract

Objective: Genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to the development of cerebral infarction (CI); however, results have been inconsistent across studies with different populations, including studies of the Chinese population. The aim of this study was to analyze the effect of MTHFR gene polymorphism on serum lipid and homocysteine levels among patients with CI in the Northwest Chinese Han population.

Patients and methods: A total of 521 CI patients and 524 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to identify MTHFR gene polymorphisms. Multivariate logistic regression analysis was used to assess the associations of MTHFR gene polymorphism with risk of CI.

Results: Frequencies of the TT genotype and the T allele were markedly higher among CI patients than among controls. After stratifying our data by sex and age, we determined that these differences in frequency of the TT genotype and the T allele were statistically significant among participants of two different age brackets and among men, but not among women (i.e., there were no statistically significant differences between female patients and female controls). CI patients and control participants with the CT or TT genotype had significantly higher homocysteine (Hcy) levels than those with the CC genotype. Among CI patients, CT/TT carriers showed significantly lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) levels as compared with CC carriers, but there was no significant difference for control participants. Multivariable logistic regression analysis showed that drinking; smoking; diabetes mellitus; levels of Hcy, direct bilirubin (DB), indirect bilirubin (IB), ApoA-I, and total protein (TP); and TT genotype were significant independent risk factors for CI.

Conclusions: The results suggested that the TT genotype of the MTHFR C677T gene polymorphism, which is associated with hyperhomocysteinemia (HHcy), might be of great clinical significance in the identification of new biomarkers for CI and in the development of individualized preventive and therapeutic strategies.

Keywords: MTHFR; Northwest China; cerebral infarction; gene polymorphism; homocysteine.

Grants and funding

This work was supported by the Natural Science Basic Research Program of Shaanxi (Program Nos. 2021-SF-130 and 2022-SF-292) and the Foundation of the First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China (Program No. 2020ZYTS-08).