Association analysis of CCL5, P2RX7, and SP110 gene polymorphisms with inactive pulmonary tuberculosis

Host genetic background plays a crucial role in Mycobacterium tuberculosis infection and the development of pulmonary tuberculosis. This study aims to investigate the association between the polymorphisms of the CCL5, P2RX7, and SP110 genes and the pathogenesis of inactive pulmonary tuberculosis.

Identify hub genes based on GEO transcriptome data. A case-control study was conducted, enrolling 154 patients with inactive Pulmonary Tuberculosis (comprising 84 untreated and 70 treated cases) and 87 controls. Peripheral blood DNA was extracted, and six polymorphic loci within the SP110, CCL5, and P2RX7 genes were genotyped using PCR and DNA sequencing. Univariate and multivariate logistic regression analyses were performed to evaluate genotypic and allelic distributions.

Two hub genes, SP110 and CCL5, were identified from the transcriptome data. At the SP110 rs9061 locus, the frequency of the A allele was lower in the untreated group compared to the control group, showing nominal significance (P = 0.015); however, this association did not remain significant after FDR correction (P_FDR  = 0.09). After adjusting for multiple factors, the A allele showed a nominally significant association with reduced IPTB risk (P = 0.042). Furthermore, although interaction (P = 0.682) and homogeneity tests (P = 0.584) were not statistically significant, limited subgroup sample sizes preclude claiming true homogeneity across subgroups. CMH stratified analysis revealed a nominally significant association (P = 0.034). Importantly, these adjusted results do not overcome the multiple-testing issue.

The A allele at the SP110 rs9061 locus may show a suggestive and exploratory association with decreased susceptibility to inactive pulmonary tuberculosis.