title: The proinflammatory cytokine TNF-alpha -308 AA genotype is associated with polyglandular autoimmunity.
abstract: Data regarding polymorphisms of immunoregulatory genes in polyglandular autoimmunity (PGA) are lacking. We have analyzed whether the polymorphism of the proinflammatory cytokine gene TNF-alpha; -308 and mutations of the autoimmune regulator (AIRE) gene were associated with PGA in adults. Sixty-seven patients with PGA and 209 healthy controls were genotyped by multiplex minisequencing with capillary electrophoresis on an ABI PRISM-310 genetic analyzer. HLA DRB1 typing was performed using polymerase-chain-reaction-amplified DNA hybridized with sequence-specific-oligonucleotide probes (PCR-SSO). The TNF-alpha; -308*A allele occurred more frequently in patients (0.269) than in controls (0.163, P = 0.008, P(c) = 0.016). Also, TNF-alpha; -308*A carriers were more frequent in patients than controls (47.8% vs. 31.1%, OR = 1.89, 95%CI = 1.19-3.00). The frequency of the AA genotype was increased in PGA (P = 0.014, P(c) = 0.042). PGA patients with autoimmune thyroid disease and the TNF-alpha; -308 AA genotype showed the highest prevalence of thyroid autoantibodies (TPO, P = 0.04; Tg, P = 0.003). HLA-DRB1*03 and TNF-alpha; -308*A alleles were strongly associated in patients with PGA (87.5%, P(c) < 0.00001). The AIRE R257X and 13bpdel mutations were not observed in patients with PGA. The association of TNF-alpha; -308*A with PGA might be directly or indirectly due to the association with HLA-DRB1*03.
authors.affiliation: Department of Medicine I, Gutenberg University Hospital, Mainz, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Dittmar
authors.forename: Adam
authors.initials: A
authors.lastname: Kaczmarczyk
authors.forename: Christian
authors.initials: C
authors.lastname: Bischofs
authors.forename: George J
authors.initials: GJ
authors.lastname: Kahaly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019075:Electrophoresis, Capillary; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000096927:AIRE Protein