Background and aim of the work: In susceptible individuals beryllium (Be)-exposure may cause Be-hypersensitivity (BH), leading to a spectrum of immune abnormalities ranging from the systemic responsiveness to Be to the CD4+ T-cell dominated chronic granulomatous pneumonitis known as berylliosis. Two gene markers have been previously associated with berylliosis: HLA-DP allelic variants carrying glutamate in position 69 of the B-chain and the high TNF-alpha production-associated TNF-alpha promoter allele TNFA2. Since a number of TNF-alpha promoter sequence variants have been associated with higher or lower gene-expression, the entire TNF-alpha promoter region was screened for BH-associated variants. Methods: Denaturating High Performance Liquid Chromatography (DHPLC) analysis followed by DNA sequence analysis of the heteroduplex observed was performed on a DNA bank obtained from a Be-exposed population composed of 73 subjects with BH and 43 Be-exposed controls. Results: The data show that the TNF-alpha TNFA2 variant (genotypic frequency: BH 26.7%, Be-exposed controls 5.8%; p < 0.0001), the -857T variant (BH 19.7%, Be-exposed controls 10.5%; p = 0.045) are significantly associated with BH and there is no linkage disequilibrium between them. Further, 64.4% of BH subjects carried at least one of higher TNF-alpha production-associated polymorphisms (Be-exposed controls 34.8%; p = 0.0036). Conclusions: The finding that TNF-alpha production-associated polymorphisms are carried at higher frequency by BH-affected compared to Be-exposed controls suggests that the TNF-alpha may play a central role in the determination of susceptibility to BH.
Dotti, C., D'Apice, M.R., Rogliani, P., Novelli, G., Saltini, C., & Amicosante, M. (2004). Analysis of TNF-alpha promoter polymorphisms in the susceptibility to beryllium hypersensitivity. SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES, 21(1), 29-34.
|Tipologia:||Articolo su rivista|
|Citazione:||Dotti, C., D'Apice, M.R., Rogliani, P., Novelli, G., Saltini, C., & Amicosante, M. (2004). Analysis of TNF-alpha promoter polymorphisms in the susceptibility to beryllium hypersensitivity. SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES, 21(1), 29-34.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/10 - Malattie dell'Apparato Respiratorio|
Settore MED/03 - Genetica Medica
|Revisione (peer review):||Sì, ma tipo non specificato|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2004|
|Titolo:||Analysis of TNF-alpha promoter polymorphisms in the susceptibility to beryllium hypersensitivity|
|Autori:||Dotti, C; D'Apice, MR; Rogliani, P; Novelli, G; Saltini, C; Amicosante, M|
|Appare nelle tipologie:||01 - Articolo su rivista|