Novel Mutaions And Polymorphisms Study Of MEF2A In Chinese Patients With Coronary Artery Disease

part I Study on novel mutations in MEF2A gene in Chinese patients with coronary artery diseaseObjective To explore the mutation of MEF2A gene in Chinese patients with coronary artery disease(CAD).Methods We investigated suspicious patients who came from Hubei,Heilongjiang,Henan,Hunan provinces clinically in Wuhan Union Hospital and Wuhan Tongji Hospital from March 1994 to Augest 1995. They were all made sure to suffer from coronary artery disease. Then we screened MEF2A gene 7 and 11 exon by polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) in 156 patients with CAD and 93 normal controls and selected probably abnormal samples to sequence .Sequencing results will be contrasted with normal sequence to ascertain the existence of mutations.Result Three mutations were found in four patients with CAD by DNA sequence analysis in the samples of abnormal mobility shift of SSCP.One mutation was 147130 (C was replaced by A,CCG/CAG) (P431Q) and the other was 21 bases deletion (147108-147128 ) which leading to the absence of 7 amino acids (424QQQQQQQ430) . They all appeared in a same patient. The above 21 bases deletion was also found in other two patients but no missense and synonymous mutation was found. The third was 147143 (G was replaced by A,CCG→CCA,proline)(coding 435)pure or heterozygous synonymous mutation in another patient. We didn't find these three mutations in controls.Conclusion Mutations of MEF2A gene existed in the patients with CAD, and the mutations were probably pathological. part II Polymorphism of MEF2A gene in Chinese patients with coronary artery diseaseObjective To detect the polymorphism of MEF2A gene in Chinese patients with coronary artery disease(CAD).Methods Polymorphism analysis of MEF2A gene was performed by use of denaturing high performance liquid chromatography (DHPLC) and polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and DNA sequencing in 156 patients with CAD and 93 normal controls.Result Polymorphisms were found in patients with CAD by DNA sequence analysis .One kind of polymorphism was 147191 (GGG→GGT, glycine)(codon 451) pure or heterozygous single nucleotide polymorphism(SNP); the other kind of polymorphism was a complex coding sequence length polymorphism in the last coding exon within a region of polyglutamine and proline repeats in 147111-147131 locus in Chinese people(one amino acid Q deletion,two amino acid QQ deletion, three amino acid QQP deletion or six amino acid QQQQQQ deletion). Conclusion Polymorphisms in exon 11 of MEF2A existed in the patients with CAD in Chinese individuals.