Analysis of TNF-α promoter polymorphisms in the susceptibility to beryllium hypersensitivity

Chiara Dotti, Maria Rosaria D'Apice, Paola Rogliani, Giuseppe Novelli, Cesare Saltini, Massimo Amicosante

Research output: Contribution to journalArticlepeer-review


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-α production-associated TNF-α promoter allele TNFA2. Since a number of TNF-α promoter sequence variants have been associated with higher or lower gene-expression, the entire TNF-α 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-α 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-α production-associated polymorphisms (Be-exposed controls 34.8%; p = 0.0036). Conclusions: The finding that TNF-α production-associated polymorphisms are carried at higher frequency by BH-affected compared to Be-exposed controls suggests that the TNF-α may play a central role in the determination of susceptibility to BH.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalSarcoidosis Vasculitis and Diffuse Lung Diseases
Issue number1
Publication statusPublished - Mar 2004


  • Beryllium-hypersensitivity
  • Genetic susceptibility
  • Granulomatous disorders
  • SNP
  • TNF-α
  • TNF-α promoter

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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