A Study On The Relationship Between IRGM Polymorphism And Pneumoconiosis Susceptiblity

Background: Pneumoconiosis is a serious occupational disease caused by the proliferation of pulmonary interstitial fibroblasts and abnormal accumulation of collagen in extracellular matrix.Studies have shown that its occurrence may be closely related to individual susceptibility.At the same time,some studies suggest that autophagy is closely related to the development of pneumoconiosis,and the immune related IRGM gene regulates the immune function of the body by inducing autophagy,thus affecting the progress of pneumoconiosis.The relationship between IRGM gene polymorphism and tuberculosis,Crohn’s disease has been studied at domestic and overseas,but whether IRGM gene polymorphism is related to susceptibility to pneumoconiosis has not been reported.Objective: To investigate the relationship between immunity related GTPase M gene polymorphism and pneumoconiosis susceptibility.Methods: 248 pneumoconiosis patients were selected as the case group,275 non-pneumoconiosis workers of similar age,sex,nationality,type of work and working age were selected as the control group.The genotypes and alleles of IRGM three SNP of were detected by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP).SNPstats software was used to analyze the correlation between single SNP and pneumoconiosis,and SHEsis software was used to analyze the linkage imbalance and haplotype of each locus.Results: There were no significant differences in the age,sex,working age,and smoking rate between the case group and the control group(P>0.05).The distribution of three SNP of IRGM gene conformed to the Hardy-Weinberg equilibrium.There is no statistical significance for the distribution of genotypes rs4958842 and rs4958843 in the case group and the control group(P>0.05).The TT,TC,CC genotype of IRGM rs4958846 have statistical significances in case group and the control group(P<0.05).The distribution frequency of TT genotype in case group is higher than that of the control group,and the distribution frequency of TC and CC genotype in control group are higher than that of the case group.Further analysis of the distribution of alleles,we found thatthere is no statistical significance for the distribution difference between case group and control group in terms of allele at IRGM rs4958842 and rs4958843(P>0.05).The distribution frequency of T allele at rs4958846 in case group is higher than that of the control group,the distribution frequency of C alleleat rs4958846 in control group is higher than that of the case group.All of the differences have statistical significance(P<0.05);After linkage disequilibrium analysis to three gene loci at rs4958842,rs4958843 and rs4958846 of IRGM,there is linkage disequilibrium between each other gene loci.Haplotype analysis was conducted on three genetic loci and established four kinds of haplotypes,the frequency distribution of ACT haplotype was significantly higher than that of the control group,while the distribution frequency of ACC haplotype was higher in the control group than in the case group(P<0.05),The distribution of other haplotypes have no statistical significances between case group and control group(P>0.05).Conclusion: The polymorphism of IRGM rs4958846 may be related to pneumoconiosis susceptibility.Workers carrying the TT genotype have an increased risk of pneumoconiosis,and the ACT haplotype is associated with the incidence of pneumoconiosis.