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 journalArticle

Abstract

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
Volume21
Issue number1
Publication statusPublished - Mar 2004

Fingerprint

Beryllium
Hypersensitivity
Berylliosis
HLA-DP Antigens
Linkage Disequilibrium
DNA Sequence Analysis
Genetic Promoter Regions
Glutamic Acid
Pneumonia
Alleles
High Pressure Liquid Chromatography
T-Lymphocytes
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Dotti, C., D'Apice, M. R., Rogliani, P., Novelli, G., Saltini, C., & Amicosante, M. (2004). Analysis of TNF-α promoter polymorphisms in the susceptibility to beryllium hypersensitivity. Sarcoidosis Vasculitis and Diffuse Lung Diseases, 21(1), 29-34.

Analysis of TNF-α promoter polymorphisms in the susceptibility to beryllium hypersensitivity. / Dotti, Chiara; D'Apice, Maria Rosaria; Rogliani, Paola; Novelli, Giuseppe; Saltini, Cesare; Amicosante, Massimo.

In: Sarcoidosis Vasculitis and Diffuse Lung Diseases, Vol. 21, No. 1, 03.2004, p. 29-34.

Research output: Contribution to journalArticle

Dotti, C, D'Apice, MR, Rogliani, P, Novelli, G, Saltini, C & Amicosante, M 2004, 'Analysis of TNF-α promoter polymorphisms in the susceptibility to beryllium hypersensitivity', Sarcoidosis Vasculitis and Diffuse Lung Diseases, vol. 21, no. 1, pp. 29-34.
Dotti C, D'Apice MR, Rogliani P, Novelli G, Saltini C, Amicosante M. Analysis of TNF-α promoter polymorphisms in the susceptibility to beryllium hypersensitivity. Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2004 Mar;21(1):29-34.
Dotti, Chiara ; D'Apice, Maria Rosaria ; Rogliani, Paola ; Novelli, Giuseppe ; Saltini, Cesare ; Amicosante, Massimo. / Analysis of TNF-α promoter polymorphisms in the susceptibility to beryllium hypersensitivity. In: Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2004 ; Vol. 21, No. 1. pp. 29-34.
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