title: TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha production.
abstract: Previous studies suggested that abnormal regulation of TNF-alpha production may have a role in the pathogenesis of rheumatic fever (RF). Polymorphism at the promoter region of TNF-alpha gene (-308 A) has recently been shown to be associated with rheumatic heart disease (RHD) in Mexican patients. Although this polymorphism has long been shown to affect TNF-alpha gene expression in cell lines, its role in production of the cytokine in RF patients has not been studied. We therefore investigated TNF-alpha G-308A single nucleotide polymorphism and its effect on TNF-alpha production in 71 Turkish RF patients and 89 ethnically matched healthy controls. The TNF-alpha-308A allele frequency was found to be significantly higher in RF patients (RHD+arthritis) than in healthy controls [p<0.0032 Odds ratio (OR)=3.4, 95% confidence interval (CI) (1.5-7.7)]. When RHD patients were analyzed as a separate group, significant difference persisted [p<0.0055, OR=3.3, 95% CI (1.5-7.6)]. More importantly, ELISPOT analysis demonstrated that existence of A allele was associated with higher TNF-alpha production compared with G allele. Our data suggest that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop RF disease.
authors.affiliation: Central Research and Immunology Laboratories, Tip Fakultesi Kampus, Antalya 07070, Turkey.
authors.forename: Nilgun
authors.initials: N
authors.lastname: Sallakci
authors.forename: Gayaz
authors.initials: G
authors.lastname: Akcurin
authors.forename: Sadi
authors.initials: S
authors.lastname: Köksoy
authors.forename: Firat
authors.initials: F
authors.lastname: Kardelen
authors.forename: Aysen
authors.initials: A
authors.lastname: Uguz
authors.forename: Mesut
authors.initials: M
authors.lastname: Coskun
authors.forename: Halil
authors.initials: H
authors.lastname: Ertug
authors.forename: Olcay
authors.initials: O
authors.lastname: Yegin
mesh_terms: D000225:Adenine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006147:Guanine / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012213:Rheumatic Fever / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine