BACKGROUND: Recently, a mutation in the human myocyte enhancer factor-2A (MEF2A) gene was reported to be responsible for an autosomal dominant form of coronary artery disease (CAD). In addition, missense mutations in sporadic CAD patients were also described. Both results support the disease-causing relationship between MEF2A and CAD/myocardial infarction. On the other hand, conflicting hypotheses have been put forward in other studies. METHODS: We screened exons 7 and 11 of MEF2A through single-stranded conformation polymorphism PCR and direct sequencing to clarify the relationship between MEF2A and CAD in an independent case-control study involving 726 individuals in China. RESULTS: Exon 11 showed a high degree of heterogeneity, which was caused by a polyglutamine (CAG)n polymorphism. Frequencies for the different (CAG)n alleles were not the same between patient and control groups. Of note, the distribution frequency of the (CAG)9 allele was higher in the patient group than in the control group (p<0.001). This effect was independent of age, gender, hypertension, diabetes mellitus, hyperlipidemia and smoking in a logistic regression model (p=0.001, odds ratio 1.245, 95% CI 1.095-1.417). It was also observed that the (CAG)9 allele was related to the extent of CAD, which was defined as no CAD, or single-, double- or triple-vessel disease (p trend 0.000). CONCLUSIONS: Based on our data, we speculate that the CAG repeat polymorphism is associated with coronary heart disease in the Chinese population and the (CAG)9 allele may be an independent predictive factor for CAD.
BACKGROUND: Recently, a mutation in the humanmyocyte enhancer factor-2A (MEF2A) gene was reported to be responsible for an autosomal dominant form of coronary artery disease (CAD). In addition, missense mutations in sporadic CAD patients were also described. Both results support the disease-causing relationship between MEF2A and CAD/myocardial infarction. On the other hand, conflicting hypotheses have been put forward in other studies. METHODS: We screened exons 7 and 11 of MEF2A through single-stranded conformation polymorphism PCR and direct sequencing to clarify the relationship between MEF2A and CAD in an independent case-control study involving 726 individuals in China. RESULTS: Exon 11 showed a high degree of heterogeneity, which was caused by a polyglutamine (CAG)n polymorphism. Frequencies for the different (CAG)n alleles were not the same between patient and control groups. Of note, the distribution frequency of the (CAG)9 allele was higher in the patient group than in the control group (p<0.001). This effect was independent of age, gender, hypertension, diabetes mellitus, hyperlipidemia and smoking in a logistic regression model (p=0.001, odds ratio 1.245, 95% CI 1.095-1.417). It was also observed that the (CAG)9 allele was related to the extent of CAD, which was defined as no CAD, or single-, double- or triple-vessel disease (p trend 0.000). CONCLUSIONS: Based on our data, we speculate that the CAG repeat polymorphism is associated with coronary heart disease in the Chinese population and the (CAG)9 allele may be an independent predictive factor for CAD.