Details

Autor(en) / Beteiligte

• Mrazek, F.
• Holla, L.I.
• Hutyrova, B.
• Znojil, V.
• Vasku, A.
• Kolek, V.
• Welsh, K.I.
• Vacha, J.
• Du Bois, R.M.
• Petrek, M.

Titel

Association of tumour necrosis factor-α, lymphotoxin-α and HLA-DRB1 gene polymorphisms with Löfgren's syndrome in Czech patients with sarcoidosis

Ist Teil von

• Tissue antigens, 2005-02, Vol.65 (2), p.163-171

Ort / Verlag

Oxford, UK, Malden, USA: Munksgaard International Publishers

Erscheinungsjahr

2005

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• :  Sarcoidosis is a granulomatous disorder showing a clear association with MHC (HLA) class I and class II genes. In order to investigate whether polymorphisms of nearby pro‐inflammatory genes located within the MHC class III region may also contribute to susceptibility to sarcoidosis or to its clinical manifestation, tumour necrosis factor‐α (TNF‐α) and lymphotoxin‐α (LT‐α) genes were chosen for analysis in a case‐control association study. In order to evaluate the findings on the TNF‐α and LT‐α genes in connection with the closely linked MHC class II region, ‘classical’ HLA‐DRB1 locus was also investigated. Polymerase chain reaction‐based methodologies were used in order to characterize two single‐nucleotide polymorphisms (TNF‐308*G/A and LTΑ+252*A/G) and HLA‐DRB1 allele groups in 114 Czech patients with pulmonary sarcoidosis and 425 healthy controls. LTA+252*G and HLA‐DRB1*13 allele carriers were more frequent in patients, compared to those in controls. By contrast, HLA‐DRB1*07 carriers were less frequent among sarcoidosis patients. The overrepresentation of TNF‐308*A, LTΑ+252*G and HLA‐DRB1*03 allele carriers was found in a subgroup of sarcoidosis patients presenting with Löfgren's syndrome (LS) by comparison with the subgroup of patients without LS (NLS; phenotype frequency LS vs NLS: 68.8 vs 37.1% for TNF‐308*A, 93.8 vs 66.3% for LTA+252*G and 68.8 vs 21.3% for DRB1*03). The data suggest that the LTΑ and HLA‐DRB1 genes themselves or a gene located nearby contributes to the susceptibility to sarcoidosis and that TNF‐308*A, LTA+252*G and HLA‐DRB1*03 alleles are associated (directly or via linkage with unknown causative locus) with LS as a specific manifestation of the disease.