title: Tumor necrosis factor-α: investigation of gene polymorphism and regulation of TACE-TNF-α system in patients with acute myocardial infarction.
abstract: A polymorphism within tumor necrosis factor-α (TNF-α) gene promoter and contribution of TNF-α converting enzyme (TACE) have been reported to be associated with TNF-α production which may increase susceptibility to heart failure such as acute myocardial infarction (AMI). However, the relationship between this polymorphism and susceptibility to AMI and the mechanism of TACE-TNF-α system regulation has poorly been studied. Genomic DNA and peripheral blood mononuclear cells (PBMCs) of patients with AMI and control subjects was extracted. The -308 G/A TNF-α polymorphism was detected. The mRNA transcription and protein expression levels of TNF-α and TACE were analyzed by real time RT-PCR and flow cytometry respectively as well as plasma TNF-α by ELISA. The 'A' allele frequency of TNF-α was significantly more frequent in the patients than controls (P < 0.001). There were statistically significant differences in TNF-α and TACE mRNA and protein levels as well as circulating TNF-α in the patients. However, these levels were higher in the patients who carry 'A' allele. There were significant positive correlation between these mRNAs and protein expression levels (r = 0.66, P < 0.001, r = 0.78, P < 0.001 respectively). These data suggest that genetic polymorphism in TNF-α might be helpful for determining susceptibility to AMI in Iranian patients. The TACE-TNF-α system in circulating leucocytes is stimulated which these results demonstrate that in patients with AMI, TACE expression in PBMC increases with TNF-α expression and processing of TNF-α in PBMC might be regulated by TACE at transcriptional, translational, and post-translational levels in AMI.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences and Health Services, Koodakyar St., Daneshjoo Blvd., Velenjak Ave., Eveen, Tehran, Iran. sghaderian@yahoo.co.uk
authors.forename: Sayyed Mohammad Hossein
authors.initials: SM
authors.lastname: Ghaderian
authors.forename: Reza
authors.initials: R
authors.lastname: Akbarzadeh Najar
authors.forename: Akram Sadat
authors.initials: AS
authors.lastname: Tabatabaei Panah
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000072198:ADAM17 Protein; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human