Cytokine gene polymorphisms in idiopathic pulmonary fibrosis.
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)-beta 1, tumour necrosis factor (TNF)-alpha 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-alpha (-308G > A) and (iv) TGF-beta 1 (Arg25Pro). The TNF-alpha (-308 A) allele was over-represented in the IPF (p(corr) = 0.004) group compared to controls. Risk of IPF was significant for heterozygotes for: (i) the TNF-alpha (-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-beta 1 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-alpha (-308 A) allele with IPF. Further research is needed to assess the utility of cytokine gene polymorphisms as markers of disease -susceptibility.
Riha
R L
RL
Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Queensland, Australia. Renata_Riha@health.qld.edu.au
Yang
I A
IA
Rabnott
G C
GC
Tunnicliffe
A M
AM
Fong
K M
KM
Zimmerman
P V
PV
D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics*; D011793:Queensland; D012795:Sialoglycoproteins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044465:White People / Q000235:genetics
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha