Association study between genetic polymorphisms in MTHFR and stroke susceptibility in Egyptian population: a...

Area of Science:

• Genetics
• Neurology
• Precision Medicine

Background:

• Stroke is a leading cause of global disability.
• Genetic factors play a crucial role in multifactorial diseases like stroke, informing precision medicine strategies.
• The methylenetetrahydrofolate reductase (MTHFR) gene is implicated in folate metabolism and has been investigated for its role in various health conditions.

Purpose of the Study:

• To investigate the association between genetic variants in the MTHFR gene and the risk of ischemic stroke in the Egyptian population.
• To determine if specific MTHFR gene polymorphisms (C677T and A1298C) are risk factors for stroke.
• To explore the relationship between these genetic variants and clinical parameters in stroke patients.

Main Methods:

• A case-control study was conducted with 100 stroke patients and 150 healthy controls from Mansoura University Hospital.
• Genomic DNA was extracted from peripheral blood, and single-nucleotide polymorphisms (SNPs) in the MTHFR gene (C677T and A1298C) were genotyped using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR).
• Statistical analysis, including odds ratios (OR) and confidence intervals, was used to assess the association between genotypes, alleles, and stroke risk under different inheritance models.

Main Results:

• The CT and TT genotypes of the MTHFR C677T polymorphism were significantly associated with an increased risk of stroke (OR 3.856, P≤0.001; OR 4.026, P≤0.001, respectively).
• The T allele of MTHFR C677T was more prevalent in stroke patients (OR 2.517, P=0.001).
• Both dominant and over-dominant models for MTHFR A1298C showed a significant association with stroke risk (P<0.001), while the recessive model did not. The CC genotype was linked to lower total cholesterol and HDL levels compared to CT+TT genotypes.

Conclusions:

• The study demonstrates a strong association between MTHFR gene mutations (rs1801133 and rs1801131) and the risk of developing ischemic stroke in the Egyptian population.
• These MTHFR gene variations, particularly C677T and A1298C, can be valuable markers for stroke prediction.
• The findings support the integration of MTHFR genotyping into personalized medicine approaches for stroke risk assessment.