Relationship Between Tumor Necrosis Factor-α Genetic Polymorphism And Idiopathic Pulmonary Fibrosis

Objective: Idiopathic pulmonary fibrosis (IPF) is an unexplained chronic inflammatory interstitial lung disease with characteristic pathological changes of usual interstitial pneumonia (UIP). IPF mainly presents diffuse alveolitis, structural disorder of alveolar units and pulmonary fibrosis, which is now considered a genetic or other aspects of patient susceptibility and the reaction against a particular disease of unknown cause, interaction between genetic factors of host and environmental exposure can lead to progressive lung injury . TNF-αas a cytotoxic factor was an active polypeptide produced by activated monocyte-macrophage cells. Recently research has proved that TNF-αgene have gene polymorphisms, and a great quantity of literatures have been reported about the relationship on hereditary susceptibility to disease between gene polymorphism of TNF-αand respiratory system disease such as pheumonia, chronic obstructive pulmonary disease, asthma and lung cancer.The studies on the relationship between gene polymorphism of TNF-αand pulmonary fibrosis disese have different results at home and abroad. The purpose of this work was to investigate the relationship between TNF-α-308 G/A genotype polymorphism and IPF of patients with Han nationality from Hebei district in China, to discuss genetic susceptibility factors and pathogenesis, and to observe the changes and effect of serum TNF-αprotein in development of IPF.Methods: 84 cases from Hebei Han nationality patients were selected by the clinical diagnosis of IPF, using population-based case-control study, according to the diagnostic criteria in《idiopathic pulmonary (interstitial) fibrosis diagnosis and treatment guidelines (draft)》issued by the respiratory chapter, the Chinese Medical Association in 2002. There were 51 male and 33female, age of 43 years to 88 years, the average age (66.7±9.5) years in present study. The cases with secondary pulmonary fibrosis, acute infection, cancer, thrombosis, heart failure, poorly controlled diabetes, peptic ulcer, severe osteoporosis, tuberculosis and IPF accepted hormones or immunosuppressive therapy were excluded. Control group included 80 Han healthy, 42 male and 38female, age of 40 years to 73 years, the average age (50.3±7.8) years and no previous history of allergic diseases, no recent infection, history of immunosuppressive agents. IPF patients and healthy controls were collected in peripheral venous 5ml. DNA of peripheral WBC was extracted by proteinase K digestion, phenol - chloroform organic solvent, resin TM genomic DNA purification kit. TNF-α-308 genetic polymorphism in promoter region was detected by PCR-RELP in control group and patients. TNF-αprotein levels in serum were measured by ELISA.Results:1 TNF-α-308 genetic polymorphism1.1 The genetype of TNF-α-308The results showed that there were three genotypes of TNF-α-308, G/G, G/A and AA. G/G was wild type, G/A and A/A were mutant type. Healthy control group and the IPF group are in line with Hardy-Weinberg genetic equilibrium test (P>0.05), with good comparability.1.2 TNF-α-308 gene polymorphism distribution between the two groups67 cases were G/G genetype, G/A genetype of 12 cases and A/A genotype of 1 case in 80 cases of the healthy control group. 57 cases were G/G genetype, G/A genetype of 22 cases and A/A genotype of 5 cases in 84 cases of the IPF group. There was significant difference between two groups on TNF-αgene polymorphism distribution (χ2=6.32, P<0.05). Odds ratio (OR) of IPF to occur of AA/GA genotype compared with GG genotype was 2.441(95% CI 1.153~5.168).1.3 TNF-αallele frequency comparison of distribution between the two groupsThe G allele frequencies was 91.3% and A allele frequencies was 8.7% in 80 cases of the healthy control group. And the G allele frequencies was 81.0% and A allele frequencies was 19.0% in 84 cases of the IPF group. There was significant difference between two groups on allele frequency of TNF-α-308 (χ2=7.207, P<0.05). Odds ratio (OR) of IPF to occur of A allele compared with G allele was 2.454(95% CI 1.256~4.796).2 TNF-αprotein levels in serumThe changes of TNF-αprotein levels in serum: TNF-αprotein levels in serum in the IPF group (10.92±2.80 ng/L) was higher than that in control group (4.95±2.11 ng/L, P<0.05).Conclusion:1 TNF-α-308 of the G/A gene polymorphism was related to IPF in Chinese Han population in Hebei, and the risk of occurrence of IPF in G/A and A/A genotype carriers is higher than those with G/G genotype. Meanwhile, in the different region and race, there are differences on the TNF-α-308 of the G/A gene polymorphism and the susceptibility of IPF.2 The level of TNF-αwas increased in IPF group, and it may take part in the pathogenesis and development of IPF.