精准医学杂志 (Dec 2024)

MTHFR gene A1298C (rs1801131) polymorphism and its correlations with cerebrospinal fluid biomarkers, cognitive level, and brain structure changes in patients with Alzheimer’s disease

  • MA Yuju, HUANG Liangyu, CHEN Jiaru, TAN Lan

DOI
https://doi.org/10.13362/j.jpmed.202406010
Journal volume & issue
Vol. 39, no. 6
pp. 514 – 518

Abstract

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Objective To investigate the relationship of A1298C (rs1801131) polymorphism in the MTHFR gene encoding methylenetetrahydrofolate reductase with the cerebrospinal fluid β-amyloid 1-42 subtype (Aβ1-42) level, cognitive level, and brain structure changes in patients with Alzheimer’s disease (AD). Methods A total of 1 271 subjects who met the inclusion criteria in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were selected. A multivariable linear regression model was used to analyze the relationship of MTHFR gene A1298C (rs1801131) polymorphism with cerebrospinal fluid Aβ1-42 level, cognitive level, and brain structure changes in AD patients. A mediation model was used to analyze the role of cerebrospinal fluid Aβ1-42 level in mediating the relationship between MTHFR gene A1298C (rs1801131) polymorphism and cognitive level. Results Multivariable linear regression model analysis showed that A1298C-C allele was negatively correlated with the level of Aβ1-42 in cerebrospinal fluid, hippocampal volume, and cognitive level (β=-0.121--0.084,t=-3.308--1.953,P<0.05), and positively correlated with cognitive status and ventricular volume (β=0.108,0.126,t=3.749,3.653,P<0.05). The mediation model showed that the level of Aβ1-42 in cerebrospinal fluid mediated 26.0% of the relationship between A1298C-C allele and memory function (ADNI_Memory score), and 19.9% of the relationship between A1298C-C allele and Mini-Mental State Examination score. Conclusion MTHFR gene A1298C (rs1801131) polymorphism affects cerebrospinal fluid biomarkers, cognitive level, hippocampal volume, and ventricular volume in AD patients. A1298C-C allele may promote the development and progression of AD by reducing the level of Aβ1-42 in cerebrospinal fluid. Targeted modification of the MTHFR gene may represent an important intervention stra-tegy for populations with a high genetic risk of AD in the future.

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