| Objective: To investigate the relationship between vitamin D levels,vitamin D receptor gene polymorphisms and treatment outcomes in tuberculosis patients.Method:Using a cohort study,taking the pulmonary tuberculosis patients treated with DOTS in Urumqi in 2019 as the research object,collecting blood samples and baseline data of the patients,and following up to observe the treatment outcome of the patients.Describe the basic information of the patient,and balance the bias of confounding factors through propensity score matching.The vitamin D level is divided into deficiency(concentration<30.0ng/m L),sufficient(concentration≥30.0ng/m L),vitamin D receptor gene polymorphism sites include Apa I(rs7975232),Bsm I(rs1544410),Fok I(rs2228570)),Taq I(rs731236),the patient’s treatment outcome includes success and failure.Chi-square test was used to analyze the correlation between vitamin D levels,vitamin D receptor gene polymorphisms and treatment outcomes in patients with different characteristics,logistic regression analysis of influencing factors of treatment failure,and consideration of the interaction between vitamin D levels and gene loci The relationship between treatment outcome,mendelian randomization was used to further analyze the causal relationship between vitamin D level and treatment outcome.Results: A total of 731 pulmonary tuberculosis patients were included,the treatment success rate of 694 patients was 94.94%,and the treatment failure rate of 37 patients was 5.06%.The average level of vitamin D in patients was 30.89±12.92 ng/m L,414 patients with vitamin D deficiency accounted for56.6%,and 318 patients with adequate vitamin D levels accounted for 43.4%.Analysis of the vitamin D levels of patients with different characteristics found that the proportion of vitamin D deficiency in the local population is higher than that of the floating population,and the proportion of vitamin D deficiency in severely ill patients is higher than that of nonserve ill patients.Univariate analysis found that the treatment failure rate of female patients was higher than that of men.The treatment failure rate of patients who were found through follow-up and referral was lower than that of other patients.Multivariate analysis found that female patients and patients found in other ways had a higher risk of treatment failure..Propensity score matching was performed on the samples to control confounding factors.After matching,the number of patients was reduced to 578,and the vitamin D deficiency and sufficient groups were 298 cases each.After matching,the data stabilized and balanced the relevant factors affecting the vitamin D level.The association analysis of vitamin D receptor gene polymorphisms on matched patients found that there was no statistically significant association between the different genotypes,alleles,and genetic patterns of the4 loci and treatment failure.After stratification of vitamin D deficiency and sufficient,patients with sufficient vitamin D levels have a higher risk of treatment failure with C/C genotype compared to C/A genotype at rs7975232;patients with vitamin D deficiency show that the risk of failure of T/T genotype therapy is increased at rs1544410,and the risk of failure of G/G genotype therapy is increased at rs731236.Analyze the interaction effect between vitamin D level and gene locus,and adjust factors such as gender.The results show that the rs7975232 locus is based on patients with C/A genotype with sufficient vitamin D levels as a reference.When the relevant factors of the patient are not adjusted,the vitamin D sufficient patients with C/C genotype,and C/A genotype with vitamin D deficiency have an increased risk of treatment failure.After adjusting for factors,patients with C/C genotype with vitamin D sufficient still have an increased risk of failure.At the rs1544410 locus,taking C/C patients with sufficient vitamin D levels as a reference,when the factors are not adjusted,the risk of treatment failure in patients with vitamin D deficiency T/T genotype is increased,and no interaction effect are found after adjusting the factors.At the rs731236 locus,taking vitamin D sufficient with A/A patients as a reference,G/G genotype patients with vitamin D deficiency have an increased risk of treatment failure when the factors are not adjusted,and no interaction effects are found after adjusting the factors.Bi-directional mendelian randomization analysis was performed to analysis the causal relationship.The vitamin D receptor gene polymorphism site was used as instrumental variable,and vitamin D level and treatment outcome were used as exposure variables and outcome variables respectively.The results did not find causal relationship between vitamin D level and treatment outcome.Conclusion: The treatment failure of pulmonary tuberculosis patients is related to the patient’s gender and the way of discovery.The interaction between vitamin D levels and vitamin D receptor gene polymorphisms is related to the outcome of pulmonary tuberculosis treatment.There is no causal relationship between the lack of vitamin D levels and treatment failure,suggesting that the gene-environment interaction has a certain modification effect on the progression of tuberculosis. |
