| BackgroundTuberculosis,a chronically and easily infectious disease commonly caused by Mycobacterium tuberculosis(M.tb),is seriously harmful to human health for a long time.According to the WHO global tuberculosis report(2016),in 2015 there were approximately 10,400,000 newly increased tuberculosis cases and about 1,400,000 people died of tuberculosis.For M.tb mainly spread through the respiratory tract and invade the lung,it is estimated that pulmonary tuberculosis accounts for about 80-90% of all tuberculosis.Therefore,this study of pulmonary tuberculosis is significant to prevent and treat tuberculosis.With the rise and population of genome-wide association study(GWAS),the association study of gene polymorphisms and susceptibility to some diseases is more and more popular.single nucleotide polymorphism(SNP)is a kind of gene polymorphism caused by the variation of single nucleotide at the genomic DNA level.And there are a large number of SNPs widely distributing through all genomic nucleic acid sequence.About 1/3 of the world's population has been infected with M.tb,but only about 5%-10% of infected persons come to be active tuberculosis.It has been reported that the polymorphisms of HLA,NRAMP1,TLR,SP110,VDR gene are associated with the morbidity of pulmonary tuberculosis with significant differences in SNP locu s among different races and different populations.The Liangshan Yi nationality has a population of more than 2'000'000.Liangshan Yi Autonomous Prefecture,the largest Yi ghettos in China,is severely tuberculosis affected area,but the association between the susceptibility to pulmonary tuberculosis and gene polymorphisms has never been reported,as well as the association between the susceptibility to pulmonary tuberculosis and the host gene polymorphism is mainly reported in Uygur,Kazak,Tibetan and the Li minority in China.suppressor of cytokine signaling 1(SOCS1)gene belongs to non HLA gene family.SOCS1 is a key molecule in the regulation of cytokine signaling pathways in macrophages during Mycobacterium tuberculosis infection.The apoptosis of macrophage is an important pathway for the clearance of M.tb,as well as the interaction of SOCS1 and mi R-155 is involved in the apoptosis of macrophage mediated by early secretory antigenic target 6(ESAT-6).The expression of SOCS1 was increased in peripheral blood mononuclear cells(PBMC)and tuberculous lymph nodes in the patients with pulmonary tuberculosis and its differential expression can also be used as an assistant in the differential diagnosis of active pulmonary tuberculosis and latent pulmonary tuberculosis.In addition,the genetic association analysis between the susceptibility to infectious diseases(chronic hepatitis B virus infection and periodontitis)and the SNPs of SOCS1 gene has been reported,while the association between the susceptibility to pulmonary tuberculosis and SOCS1 SNPs has never been reported.So in the project study we suppose that SOCS1 SNPs are associated with the susceptibility to pulmonary tuberculosis in the Liangshan Yi population.ObjectiveTo investigate the genetic association between two tag SNP polymorphisms of SOCS1 gene named-3969C/T(rs243327)and +1125G/C(rs33932899)and the occurrence of pulmonary tuberculosis in the Yi population in Liangshan.MethodsIn Case control study,from March 2015 to June 2016,304 newly diagnosed pulmonary tuberculosis patients(PTBs)were randomly enrolled in Changan branch courts in the First People's Hospital in Liangshan Yi Autonomous Prefecture,while 310 apparent healthy controls(HCs)were enrolled in Xichang People's Hospital,the PLA 519 th Hospital and Xichang Meinian Health Examination Center.Two tag SNP polymorphisms of SOCS1 gene named rs243327 and rs33932899 were analyzed by gene sequencing.The Hardy-Weinberg Law of genetic equilibrium was used to detect the representativeness of the sample group,and the Mann-Whitney U test was used to compare the age,while the Chi-square test was used to the difference of gender and smoking history between PTBs and HCs.The genotype and allele frequency of two tag SNPs in co-dominant model,dominant model,recessive model,super dominant model and additive model could be determined by Chi-square test and non-conditional Logistic Regression Analysis.Results1.In this study,304 PTB cases in the Liangshan Yi population were randomly selected,with an average age of 35.83±16.22 yr,with male patients 65.79% of total.And 310 healthy controls were enrolled,with an average age of 38.72±13.15,with male patients 60.64% of total.There was no significant difference in gender and age distribution between the two groups(P=0.186,P=0.224),gender and age were not associated with the risk of pulmonary tuberculosis among the Yi population in Liangshan.2.The success rate was 100%,because of rs243327 and rs33932899 loci were classified by PCR-gene sequencing.The polymorphism of Allele C? Allele T is in rs243327 loci while the polymorphism of Allele G? Allele C is in rs33932899 loci.Both rs243327 and rs3393289 show no deviation from Hardy-Weinberg equilibrium(HWE)in either PTB group or the HCs(rs243327:P=0.070,P=0.229;rs33932899: P=0.869,P=0.109).3.There was a significant correlation between rs243327 polymorphism and the risk of pulmonary tuberculosis,and the frequency of CC genotype in PTB group is higher th an that in HCs(CC vs CT:X~2=4.248,OR=1.449,95% CI=1.018-2.063,P=0.039;CC vs CT+TT:X~2 =5.179,OR=1.472,95%CI=1.54-1.056,P=0.023;additive model: OR=0.649,95%CI= 0.433-0.973,P=0.037),meanwhile the frequency of C allele is also higher than that in HCs(C vs T:X~2=5.343,OR=1.391,95%CI=1.051-1.841,P=0.021).4.There was no significant correlation between rs33932899 polymorphism and pulmonary tuberculosis(GG vs GC:X~2=0.031,OR=1.031,95%CI=0.730-1.456,P=0.861;GG vs CC:X~2=2.595,OR=1.856,95%CI=0.866-3.986,P=0.107;GG vs GC vs CC: X~2= 2.601,P=0.272;GG+GC vs CC:X~2=2.570,OR=1.837,95%CI=0.865-3.902,P=0.109;GG vs GC+CC:X~2=0.429,OR=1.116,95%CI=0.803-1.551,P=0.513;GC vs GG+CC: X~2=0.006,OR=1.013,95%CI=0.721-1.425,P=0.939;additive model: OR=1.181,95%CI= 0.786-1.774,P=0.422;G vs C:X~2=1.349,OR=1.178,95% CI= 0.893-1.553,P=0.245).5.Smoking is an independent risk factor for pulmonary tuberculosis because there was a significant correlation between smoking history and risk of pulmonary tuberculosis in the Liangshan Yi population(X~2=16.982,OR=2.010,95%CI= 1.439-2.808,P=0.000).The risk of pulmonary tuberculosis in the Liangshan Yi population with a history of smok ing was 2.010 times higher than that without smoking history.ConclusionsIt is the first time to evaluate the genetic association between SOCS1 gene single nucleotide polymorphism and the susceptibility to pulmonary tuberculosis in the Yi population in Liangshan.The study shows that there is a significant genetic association between-3969 C/T(rs243327)loci and the risk of pulmonary tuberculosis,with the genotype of CC and the allele C increase the risk of pulmonary tuberculosis in the Yi population in Liangshan.However,there may be no significant genetic association between +1125G/C(rs33932899)loci and pulmonary tuberculosis.These research results not only provide the theoretical basis for further study which the different C/T alleles at rs24332 7 loci regulates SOCS1 gene expression,but also lays a theoretical foundation for predicting the risk of pulmonary tuberculosis and improving the level of prevention and treatment of pulmonary tuberculosis,and to find a new molecular target for the predi ction and diagnosis of pulmonary tuberculosis. |
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