ArticleBMC cardiovascular disorders2026
Association between MEF2A variants and ischemic stroke risk: a case-control study and two prospective cohort studies in a Chinese population.
Article in BMC cardiovascular disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTranscriptional regulators encoded by the myocyte enhancer factor 2 (MEF2) gene family play a crucial role in cardiac development, homeostasis, and pathology. The relationship between MEF2A and ischemic stroke (IS) remains unclear.
methodsWe performed MEF2A polymorphism genotyping in a case-control study (2497 patients with IS vs. 3135 controls) and a cohort study involving 4080 non-stroke participants, which included up to 11.54 years of follow-up. Additionally, the mortality outcomes of 2298 patients with IS were followed up for 6.49 years. Furthermore, 301 IS and 313 controls were selected from the case-control study for MEF2A mRNA expression quantification using RT-qPCR. The modified Rankin Scale (mRS) scores of IS at the time of discharge and, one, three, six month post-discharge was collected. Multiple Cox regression analyses were used to estimate the hazard ratio (HR) with 95% confidence interval (CI). Restricted cubic spline (RCS) regression analyses were used to evaluate the dose-response relationship between mRNA expression levels and IS. Linear mixed-effects models were applied to examine the associations of the two SNPs and mRNA expression with the mRS scores.
resultsCarriers of the 2292288-rs3743248 G-T haplotype had a higher IS risk compared with carriers of the G-C haplotype; OR (95% CI]) were as follows: 1.417(1.120, 1.792), 1.581 (1.172, 2.133), 1.314 (0.991, 1.741) for patients with IS, large-artery atherosclerosis subtype, small-artery occlusion, respectively. Sex-stratified analysis identified rs2292288-AA as a female-specific risk factor for IS prevalence (HR = 1.755, 95% CI: 1.179–2.613), while in patients > 65 years, A-allele carriers showed worse functional recovery (higher mRS, P = 0.012). There was a non-linear correlation between MEF2A mRNA expression level and IS risk (Pnonlinear= 0.001), after adjustment for covariates.
conclusionsOur findings indicate that the MEF2A G-T haplotype is associated with IS susceptibility. While the rs2292288 variant demonstrates sex-specific effects on disease incidence and age-specific effects on recovery. Lower MEF2A mRNA expression was associated with an increased IS risk.
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