Study On The Relationship Between Environmental Factors And TAP Gene Polymorphisms And Susceptibility To Tuberculosis Based On Tuberculosis Families

Objective Tuberculosis(TB)is global public health event,China has a high burden of TB.As a large population province,Guangdong Province has frequent personnel flow,and the situation of TB prevention and control is still a grim struggle.Tuberculosis is closely related to pathogens,host genetic factors,environmental factors and other factors,and there may be complex interaction among these factors,but there are few reports.Therefore,the study of single nucleotide polymorphism and environmental risk factors of transporter associated with antigen processing(TAP)gene in Han population in Guangdong Province will help us understand the pathogenesis of tuberculosis and to carry out precise control as soon as possible.Methods Based on the case-control study method in tuberculosis multiple families,413 subjects were included in 150 families,of which75 TB families and 75 health control families were respectively,including133 tuberculosis patients,107 close contacts from healthy families,and173 healthy controls.The results showed that the family of the study subjects were interviewed to assess the environmental factors,blood samples were collected and DNA was extracted.The genotypes of TAP1gene(rs1135216,rs1057141)and TAP2(rs3819721 and rs241447)were genotyped by Taq Man probe method.Hardy Weinberg test was used to analyzes whether each genetic variation conforms to HWE genetic balance law.The single factor analysis was carried out by chi square test,and the correlation between the influencing factors and tuberculosis was analyzed by logistic regression.The interaction of gene-gene and geneenvironment was analyzed by MDR method,and the combination of risk factors was selected.Results Compared with the healthy family control group,the results were as follows: 1.The proportion of male,BMI≤18.5,primary school and below,physical labor for occupation and rural household registration were 68.4%,22.6%,33.1%,56.4% and 60.2% respectively in TB group;the proportion of smoking history,irregular fitness activities and uninfected BCG vaccine in TB group was 50.4%,68.4% and 69.2%;The proportion in TB group of more than 2 people live in one bedroom,and indoor lighting was poor indoor humidity and poor sanitation was 78.9%,40.6%,74.4% and 34.6%,respectively.The results of multivariate analysis showed that the incidence risk of tuberculosis with BMI≤18.5was 3.941 times higher than that of BMI>18.5(95% CI=1.616-9.610),the incidence risk of tuberculosis in smokers was 2.380 times(95%CI=1.099-5.153)than that of non-smokers,and the risk of indoor moist was 2.4 times(95% CI=1.156-4.982);The risk of tuberculosis can be reduced by regular exercise activities,non-manual occupation,vaccination of BCG,living number of bedrooms≤1 person,and good indoor environment hygiene.The results of association analysis between polymorphisms and tuberculosis showed that TC+CC genotype was 1.89 times of the risk of TT genotype for rs1135216(95% CI=1.03-3.48),and for rs3819721,the main risk factor was carrying AA genotype,which was4.88 times of the risk of carrying GG gene(95% CI=1.44-16.60).GA+AA and AG genotype were secondary risk factors,which were 3.55 times and 3.33 times of the risk of carrying GG genotype.The linkage imbalance analysis showed that there was a certain degree of linkage imbalance among the four loci(P < 0.05).Among the haplotypes constructed,the prevalence risk of haploid in TB group was 5.85,7.06 and 11.88 times higher than that of TGTT haploid.MDR analysis of gene-gene showed that rs1057141,rs3819721 and rs241447 were used to obtain the best model.1000 replacement tests were statistically significant(P< 0.001),the consistency of cross validation(CVC)was8/10,the prediction accuracy(TA)was 0.6671.The best model of geneenvironment interaction was the three factors model of occupation,smoker and fitness activity.The result showed that the consistency of cross validation(CVC)was 10/10,and the best prediction accuracy(TA)was 0.7433.2.compared with the HHC group,multivariate analysis showed that the risk of tuberculosis under 45 years old was 5.743 times higher than that of 60 years old(95% CI=2.014-16.378),and the risk of tuberculosis in primary school and below was 5.011 times higher education level(95% CI=2.107-11.915),and 4.411 times higher than that of non-smokers(95% CI=1.861-10.460),with exercise activities,can reduce the risk of tuberculosis,and it is a protective factor of TB(OR=0.260,95%CI=0.132-0.511).The results of association analysis between polymorphism and tuberculosis showed that TC+CC genotype was 2.07 times higher than that of TT genotype(95% CI=1.07-4.00)for rs1135216.The results of MDR analysis showed that rs3819721 and rs1135216 with two genes were the best models.1000 replacement tests were statistically significant(P < 0.001),the consistency of cross validation(CVC)was8/10,and the prediction accuracy(TA)was 0.6343.However,no obvious interaction between gene and environment was found.Conclusion 1.Compare with the general population,BMI≤18.5,smokers and indoor humidity may be the main risk factors for TB families.Regular fitness activities,non-manual occupation,vaccination of BCG vaccine,living in bedrooms lower than 1 person,and good indoor environment hygiene are the protective factors of TB.Compared with HHC,the risk factors of tuberculosis are under 45 years old,education level below primary school,smoking history,regular fitness activities are protective factors of TB.2.The rs1135216 and rs3819721 of TAP1 gene are significantly related to the infection and incidence of tuberculosis.The TC+CC genotype of rs1135216 and AA of rs3819721 may be the high-risk genotype of tuberculosis.It is suggested that the locus rs1135216 of TAP1 gene and rs3819721 of TAP2 gene may be candidate for tuberculosis in tuberculosis multiple families of Han population in Guangdong Province.3.Compared with the general population,the role of three genes including rs1057141,rs3819721 and rs241447 were the best model.The role of three factors including occupation,smoking history and fitness activities were also high-risk models of morbidity of tuberculosis.Compared with HHC population,rs3819721 and rs1135216 were high risk models of tuberculosis.