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Updated: May 30, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Evaluation of the MTHFR A1298C variant in leukoaraiosis
Zoltan Szolnoki1, Istvan Szaniszlo, Marta Szekeres
1Department of Neurology and Cerebrovascular Diseases, Pándy Kálmán County Hospital, Gyula, Hungary. szolnoki99@hotmail.com
Insights
The methylenetetrahydrofolate reductase (MTHFR) A1298C genetic variant is an independent risk factor for leukoaraiosis (LA), a brain condition linked to cognitive decline. This risk is amplified when combined with the MTHFR C677T variant.
Area of Science:
- Neurology
- Genetics
- Vascular Biology
Background:
- Leukoaraiosis (LA) is common brain white matter demyelination associated with cognitive decline.
- Elevated serum homocysteine levels are linked to LA, alongside hypertension and aging.
- The MTHFR C677T variant affects homocysteine but its independent role in LA is unproven.
Purpose of the Study:
- To investigate the association between the MTHFR A1298C genetic variant and the presence of leukoaraiosis (LA).
- To determine if MTHFR A1298C is an independent risk factor for LA.
- To assess the combined effect of MTHFR A1298C and MTHFR C677T variants on LA risk.
Main Methods:
- Analysis of clinical and genetic data from 198 LA patients and 235 healthy controls.
- Genotyping for MTHFR A1298C and MTHFR C677T variants.
- Statistical comparison of variant frequencies between LA patients and controls.
Main Results:
- The MTHFR A1298C variant (A1298C or 1298CC genotypes) was a significant risk factor for LA compared to the absence of these variants.
- Co-occurrence of heterozygous MTHFR A1298C and C677T variants increased the risk of LA.
- The MTHFR A1298C variant demonstrated an independent genetic risk for LA.
Conclusions:
- The MTHFR A1298C genetic variant is an independent risk factor for leukoaraiosis.
- The pathological role of MTHFR A1298C in LA may be potentiated by the presence of the MTHFR C677T variant.
- These findings highlight the genetic contribution of MTHFR variants to leukoaraiosis and cognitive decline.
Abstract:
Vascular demyelinization of the white matter of the brain is referred to as leukoaraiosis (LA). This very frequent entity is associated with a cognitive decline, thereby resulting in a deteriorating quality of life. Besides poorly controlled hypertension and aging, its development is reported to be associated with an elevated serum homocysteine level. Although the methylenetetrahydrofolate reductase (MTHFR) C677T genetic variant is associated with an elevated serum homocysteine level, it has not been proved to be an independent risk factor for LA. The aim of the present study was to examine whether the MTHFR A1298C genetic variant, which is also believed to be unfavorable, is associated with the presence of LA. The clinical and genetic data on 198 LA patients and 235 neuroimaging alteration-free controls were analyzed. The presence of the A1298C or the 1298CC variant was calculated to be a risk factor for LA, as compared with the absence of both of them. The clustering of the heterozygous A1298C and C677T variants was proved to involve the risk of LA. Our results suggest that the MTHFR A1298C variant confers an independent genetic risk of LA, and this pathological role may be amplified by the MTHFR C677T variant.
