Cytokine gene polymorphisms in idiopathic pulmonary fibrosis

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Abstract:

Abstract

Pro- and anti-fibrotic cytokine gene polymorphisms may affect expression of idiopathic pulmonary fibrosis (IPF). The aims of the present case-control study were to examine polymorphisms in the IL-6, transforming growth factor (TGF)-β1, tumour necrosis factor (TNF)‐α and interleukin-1 (IL-1)Ra genes in patients with IPF (n = 22) ­compared to healthy controls (n = 140). Genotyping was performed on DNA extracted from peripheral blood lymphocytes, using polymerase chain reaction − restriction fragment length polymorphism with gene polymorphisms determined according to ­published techniques. The following sites were examined: (i) IL-1Ra*1−5 (86 bp variable tandem repeat intron 2), (ii) IL-6 (−174G > C), (iii) TNF-α (−308G > A) and (iv) TGF-β1 (Arg25Pro). The TNF-α (−308 A) allele was over-represented in the IPF (pcorr = 0.004) group compared to controls. Risk of IPF was significant for heterozygotes for: (i) the TNF-α (−308 A) allele (A/G) (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2−7.2; P = 0.02), (ii) homozygotes (A/A) (OR 13.9; 95%CI 1.2−160; P = 0.04) and (iii) carriage of the allele (A/A + A/G) (OR 4; 95%CI 1.6−10.2; P = 0.003). The distribution of alleles and genotypes for IL-6, TGF-β1 and IL-1Ra between the two groups was not significantly different. This is the third study to independently confirm that there is a significant association of the TNF-α (−308 A) allele with IPF. Further research is needed to assess the utility of cytokine gene polymorphisms as markers of disease ­susceptibility. (Intern Med J 2004; 34: 126−129)

Keywords: TNF-α; cytokine gene ­polymorphism; genotype; interstitial lung disease

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1444-0903.2004.00503.x

Affiliations: 1: Department of Thoracic Medicine, The Prince Charles Hospital and 2: Department of Medicine, University of Queensland, Brisbane, Queensland, Australia

Publication date: March 1, 2004

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