Riha R L, Yang I A, Rabnott G C, Tunnicliffe A M, Fong K M, Zimmerman P V
Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Queensland, Australia.
Intern Med J. 2004 Mar;34(3):126-9. doi: 10.1111/j.1444-0903.2004.00503.x.
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.
促纤维化和抗纤维化细胞因子基因多态性可能会影响特发性肺纤维化（IPF）的表达。本病例对照研究的目的是检测IPF患者（n = 22）与健康对照者（n = 140）白细胞介素（IL）-6、转化生长因子（TGF）-β1、肿瘤坏死因子（TNF）-α和白细胞介素-1（IL-1）受体拮抗剂（IL-1Ra）基因的多态性。采用聚合酶链反应-限制性片段长度多态性方法，根据已发表的技术对从外周血淋巴细胞中提取的DNA进行基因分型，检测以下位点：（i）IL-1Ra*1-5（86 bp可变串联重复序列内含子2），（ii）IL-6（-174G＞C），（iii）TNF-α（-308G＞A）和（iv）TGF-β1（Arg25Pro）。与对照组相比，IPF组中TNF-α（-308 A）等位基因的比例过高（校正P值 = 0.004）。对于以下情况的杂合子，IPF风险显著：（i）TNF-α（-308 A）等位基因（A/G）（比值比（OR）2.9；95%置信区间（CI）1.2 - 7.2；P = 0.02），（ii）纯合子（A/A）（OR 13.9；95%CI 1.2 - 160；P = 0.04），以及（iii）携带该等位基因（A/A + A/G）（OR 4；95%CI 1.6 - 10.2；P = 0.003）。两组之间IL-6、TGF-β1和IL-1Ra的等位基因和基因型分布无显著差异。这是第三项独立证实TNF-α（-308 A）等位基因与IPF存在显著关联的研究。需要进一步研究以评估细胞因子基因多态性作为疾病易感性标志物的效用。
