title: The role of tumor necrosis factor alpha G-308A polymorphisms in the course of pulmonary sarcoidosis.
abstract: This study was designed to evaluate the relationship between the presence of tumor necrosis factor (TNF) polymorphisms, human leukocyte antigen (HLA)-DRB1*03 linkage and the prognosis of sarcoidosis. In a retrospective case-control study, TNF-alpha G-308A, TNF-alpha G-238A, lymphotoxin-alpha (LTA) and HLA-DRB1*03 were genotyped in 625 sarcoidosis patients. These patients were classified into 298 patients with persistent disease and 327 patients with non-persistent disease using chest X-ray (CXR) appearances and lung function parameters after at least 2 years of follow-up. The TNF-alpha-308A variant allele was observed in 25.5% of patients with persistent disease compared with 44.0% of patients with non-persistent disease. The corresponding odds ratio (OR) was 0.43 with a 95% confidence interval (CI) of 0.30-0.61. A strong linkage was found between TNF-alpha G-308A and HLA-DRB1*03 (OR = 0.03, 95% CI: 0.02-0.05). For TNF-alpha G-238A and LTA NcoI A252G, there were no statistically significant differences in the distribution of genotypes between the groups with and without persistent disease. The data indicate that presence of a TNF-alpha-308A variant allele and HLA-DRB1*03 were associated with a favorable prognosis. Because of the strong linkage between TNF-alpha G-308A and HLA-DRB1*03, genotyping of one simple and less expensive TNF-alpha single nucleotide polymorphism can be used to predict the prognosis of pulmonary sarcoidosis in clinical practice.
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: P A
authors.initials: PA
authors.lastname: Wijnen
authors.forename: P J
authors.initials: PJ
authors.lastname: Nelemans
authors.forename: J A
authors.initials: JA
authors.lastname: Verschakelen
authors.forename: O
authors.initials: O
authors.lastname: Bekers
authors.forename: C E
authors.initials: CE
authors.lastname: Voorter
authors.forename: M
authors.initials: M
authors.lastname: Drent
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D012507:Sarcoidosis / Q000235:genetics; D017565:Sarcoidosis, Pulmonary / Q000000981:diagnostic imaging / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014965:X-Rays
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha