The Association Study Of VitD Levels And VDR Gene Polymorphisms On Latent TB Infection Of Close Family Contacts With TB

Objective: Based on the population of close contacts of active TB families,explore and analyze the relationship between the Vit D level,VDR gene polymorphism and their interaction and the latent TB infection,and provide reference and methodological support for moving forward the threshold of tuberculosis prevention and control,accurately screening the latent infection,and preventing and controlling the spread of TB.Methods:Cross sectional investigation and convenient sampling method were used to collect 417 close family contacts of TB patients in Urumqi and Karamay,Xinjiang,and to conduct symptom screening,chest X-ray screening,and TST testing to determine whether they were latent TB infection;Using a questionnaire survey to collect the basic information of research subjects,basic information of indicated cases,close contact status,personal protective behavior,family living environment,and other environmental exposure related influencing factors;Blood was extracted for Vit D level detection using enzyme-linked immunosorbent assay,and VDR gene polymorphism was detected using Mass ARRAY SNP genotyping technology.Three are 3 parts of the study:1)Describe and analyze the current status of latent TB infection among close family contacts,and use univariate and multivariate logistic regression to analyze the environmental exposure influencing factors of latent TB infection.2)Based on multiple factor analysis,different genetic patterns,linkage disequilibrium,and haplotypes,environmental exposure factors were controlled to analyze the serum Vit D levels and the association between VDR and latent TB infection.Multiple factor dimensionality reduction analysis was used to investigate the impact of higher-order interactions between VDR genes,Vit D levels VDR genes,and environmental factors Vit D levels VDR genes on latent TB infection in close family contacts.3)Construct a Bayesian network structure to analyze and reveal the complex network relationships between environmental influencing factors,Vit D levels,and VDR gene polymorphisms,as well as the causal associations between latent TB infections.Result: 1)The latent TB infection rate in the study subjects was 32.37%(135/417).Single factor analysis showed a correlation between occupational type and latent TB infection(P<0.05);In the household living environment of the subjects,the single factor analysis showed that the use of activated carbon was associated with the latent TB infection(P<0.05),After principal component analysis,four dimensions were separated.The univariate analysis dimensions of "ventilation status","disinfection and sterilization in the room" and "home furnishings" were associated with latent TB infection(P<0.05);The logistic regression model shows that the study subjects were manual workers(OR=0.551,95% CI: 0.362-0.838)and the good condition of disinfection and sterilization in the house(OR=0.410,95% CI: 0.205～0.819)are protective factors for latent TB infection.2)The levels of Vit D and gene frequencies in various genetic patterns of VDR gene SNP loci were not associated with latent TB infection(P>0.05);The alleles at each SNP locus and subsequent construction of haploids had no effect on latent TB infection(P>0.05).In multivariate analysis,positive bacteriological results(OR=1.486,95%CI:1.064～2.077)and allele A at the Apa I locus(OR=1.437,95%CI:1.009～2.047)were risk factors for latent TB infection.In higher-order interactions,VDR gene self-interaction and Vit D level-VDR gene interaction had no effect on latent TB infection(P>0.05);The high-order interaction between environmental factors,Vit D levels and VDR genes has an impact on the latent TB infection(P<0.05).3)Bayesian network causal inference of latent TB infection shows that the combined effect of VDR genes results in a maximum decrease of 17% and a maximum increase of 44% in the latent TB infection rate;When environmental factors are protective factors,the combined effect of VDR genes results in a maximum decrease of 4% in the latent TB infection rate;When environmental factors are risk factors,the combined effect of VDR genes increases the latent infection rate of TB to a maximum of 75%;That is,the combination of environmental factors(occupation,home disinfection and sterilization,bacteriological detection of indicator cases)and VDR gene has an impact on the latent TB infection.The difference in structure and probability of constructing Bayesian networks with different levels of Vit D is small,and the combined regulatory effect of serum Vit D levels on genes and environment is not significant.Conclusion: The Apa I allele of the VDR gene and environmental exposure factors have an impact on the latent TB infection rate in close family contacts,but they exhibit complex network interaction effects.The correlation between Vit D levels and latent TB infection needs further research,and the regulatory effect of Vit D levels needs further large-scale research to clarify.The use of multifactor dimensionality reduction analysis combined with Bayesian network inference methods will help identify combinations with strong combined effects of gene and environmental exposure,providing reference and methodological support for precise prevention and control of latent TB infections.