关键词: 结核, 基因, 多态性, 单核苷酸, 疾病遗传易感性

Abstract:

Objective: To investigate the association between genetic polymorphisms in the stimulator of interferon genes (TMEM173), interferon gamma receptor 1 (IFNGR1), interferon gamma receptor 2 (IFNGR2), and interferon regulatory factor 8 (IRF8) and tuberculosis susceptibility. Methods: A case-control study was conducted, including 286 pulmonary tuberculosis cases (Observation group) admitted to Shanghai Pulmonary Hospital from January 2020 to December 2022 and 484 healthy individuals (Control group). Peripheral venous blood was collected from both groups for genomic DNA extraction, genetic analysis and single nucleotide polymorphism (SNP) screening. Genotyping was performed using the SNPscan^TM multiplex SNP genotyping assay. Logistic regression and Chi-square tests were used to compare differences in allele, genotype, and haplotype frequencies between the observation and control groups. Associations between SNPs and tuberculosis susceptibility were analyzed under dominant, recessive, and over-dominant genetic models. Multivariate logistic regression was performed to analyze the association between the interaction among SNPs and tuberculosis susceptibility. Results: All SNP allele frequency distributions conformed to Hardy-Weinberg equilibrium. Carriers of the rs8064189 T allele (OR=1.290, 95%CI: 1.047-1.590, P=0.017), TT genotype (OR=1.689, 95%CI: 1.098-2.597, P=0.017), GT-TT genotype (OR_dominant=1.231, 95%CI: 0.999-1.517, P=0.047) and rs805252 (OR=1.628, 95%CI: 1.033-2.565, P=0.035;OR_recessive=1.306, 95%CI: 1.037-1.645, P=0.037), as well as the CTGAA haploid type (OR=1.271, 95%CI: 1.078-1.513, P=0.011) of IRF8 gene significantly increased the tuberculosis risk. Rs9808753 AG genotype (OR=1.450, 95%CI: 1.038-2.025, P=0.029) and AA-GG genotype (OR_{hyper-dominance}=0.807, 95%CI: 0.671-0.970, P=0.025) of IFNGR2 gene also significantly increased the risk of tuberculosis. The IFNGR1 TTGG haplotype (OR=1.160, 95%CI: 1.014-1.350, P=0.047) was linked to increased tuberculosis susceptibility. Multivariate logistic regression revealed that the CT genotype in TMEM173 gene rs7380824 increased the tuberculosis risk by 1.431-fold. (OR=1.431, 95%CI: 1.034-1.979, P=0.031). No significant associations were observed between tuberculosis susceptibility and other SNPs. Conclusion: TMEM173, IFNGR1, IFNGR2, and IRF8 genes may serve as susceptibility genes for tuberculosis in the Chinese population.

Key words: Tuberculosis, Gene, Polymorphisms, single nucleotides, Genetic predisposition to disease