Impact of the Polymorphism of the PACRG and CD80 Genes on the Development of the Different Stages of Tuberculosis Infection

Tuberculosis (TB) is one of the most significant health-care problems worldwide. The host’s genetics play an important role in the development of TB in humans. The disease progresses through several stages, each of which can be under the control of different genes. The precise genes influencing the different stages of the disease are not yet identified. The aim of the current study was to determine the associations between primary and secondary TB and the polymorphisms of novel candidate genes for TB susceptibility, namely CD79A, HCST, CXCR4, CD4, CD80, CP, PACRG, and CD69. A total of 357 patients with TB (130 cases with primary TB and 227 cases with secondary TB) from the Siberian region of Russia as well as 445 healthy controls were studied. The study was performed at the Research Institute of Medical Genetics, Tomsk NRMC, Tomsk, Russia, between July 2015 and November 2016. Genotyping was carried out using MALDI-TOF mass spectrometry and PCR-RFLP. The associations between the single-nucleotide polymorphisms and TB were assessed using logistic regression adjusting for covariates (age and gender). Multiple testing was addressed via the experiment-wise permutation approach. The statistical significance threshold was a P value less than 0.05 for the permutation P values. The analyses were done in R 3.2 statistical software. An association was established between the rs1880661 variant of the CD80 gene and secondary TB and the rs10945890 variant of the PACRG gene and both primary and secondary TB. However, the same allele of PACRG appeared to be both a risk factor for reactivation (secondary TB) and a protector against primary infection. The results suggested that the CD80 and PACRG genes were associated with susceptibility to different forms of TB infection in the Russian population.