Research Article

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis

Published: December 19, 2013
Genet. Mol. Res. 12 (4) : 6882-6894 DOI: https://doi.org/10.4238/2013.December.19.7
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Abstract

Several independent studies have reported the role of the methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism in strokes, but the results are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed in the present study. In this meta-analysis, a total of 13 studies, including 1974 cases and 2660 controls, were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association in additive, dominant, and recessive models. The overall analysis showed that MTHFR A1298C was associated with a significant increase in the risk of stroke in the heterozygote comparison (AC vs AA: OR = 1.17; 95%CI = 1.03-1.34) and in the dominant model (AC/CC vs AA: OR = 1.22; 95%CI = 1.01-1.49). Stratified analysis showed a significantly strong association between the MTHFR A1298C polymorphism and stroke risk in Asian populations (OR = 1.32 for AC vs AA; OR = 1.94 for CC vs AA; OR = 1.37 for AC/CC vs AA; OR = 1.33 for C vs A allele), but not in Caucasian populations. Additionally, the MTHFR 1298C allele was found to be a risk factor for developing ischemic strokes. However, no statistically significant increased risk of hemorrhagic stroke was found in any of the genetic models. In conclusion, this meta-analysis supported that the MTHFR A1298C polymorphism could be capable of increasing stroke susceptibility in Asian, but not in Caucasian, populations.

Several independent studies have reported the role of the methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism in strokes, but the results are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed in the present study. In this meta-analysis, a total of 13 studies, including 1974 cases and 2660 controls, were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association in additive, dominant, and recessive models. The overall analysis showed that MTHFR A1298C was associated with a significant increase in the risk of stroke in the heterozygote comparison (AC vs AA: OR = 1.17; 95%CI = 1.03-1.34) and in the dominant model (AC/CC vs AA: OR = 1.22; 95%CI = 1.01-1.49). Stratified analysis showed a significantly strong association between the MTHFR A1298C polymorphism and stroke risk in Asian populations (OR = 1.32 for AC vs AA; OR = 1.94 for CC vs AA; OR = 1.37 for AC/CC vs AA; OR = 1.33 for C vs A allele), but not in Caucasian populations. Additionally, the MTHFR 1298C allele was found to be a risk factor for developing ischemic strokes. However, no statistically significant increased risk of hemorrhagic stroke was found in any of the genetic models. In conclusion, this meta-analysis supported that the MTHFR A1298C polymorphism could be capable of increasing stroke susceptibility in Asian, but not in Caucasian, populations.

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