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Cytokine gene polymorphisms in idiopathic pulmonary fibrosis


  • Funding: R. L. Riha was supported in part by the JT Tweddle Fellowship, 2000, which was granted by the Royal Australasian College of Physicians and does not pose conflict of interest for any of the authors.

    Conflicts of interest: None

Renata L Riha, The Prince Charles Hospital, Chermside, Qld 4053, Australia. Email:



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)