Patient single nucleotide polymorphisms assiocated with Mycobacterium tuberculosis genotypes in Ugandan population

Abstract

Uganda is one of the 30 World Health Organization-designated countries with a high burden of TB/HIV, with three main dominant genotypes that cause tuberculosis. Recent studies have shown that the M. tuberculosis Uganda genotype has been predominant for the past 20 years. However, the reason for its prevalence is unknown. In our study, we used the host factors to explain why the M. tuberculosis Uganda genotype is the most predominant. The study determined M. tuberculosis main lineages and sub-lineages and the host Single Nucleotide Polymorphisms associated with specific M. tuberculosis lineages. Mycobacterium tuberculosis isolates Deoxyribonucleic acid was genotyped using M. tuberculosis lineage-specific Single Nucleotide Polymorphisms deletion primers for the presence of main and sub-lineages. Genomic Deoxyribonucleic acid was genotyped using a MassARRAY for the presence of host Single Nucleotide Polymorphisms. In the analysis, genetic data was paired with the corresponding M. tuberculosis lineage and imputed in Statistical Package for the Social Sciences software. A total of 70 isolates were analyzed for Mycobacterium tuberculosis lineages. Of which 50 % were lineage 4 Uganda genotype, 36 % were lineage 3 genotype, 4 % were other lineage 4 strains, and 10% were mixed lineages. Of the 70 isolates, 30 were removed and, one isolate failed. A total of 39 isolates were genotyped at 11 Single Nucleotide Polymorphisms. All the 11 Single Nucleotide Polymorphisms were not associated with Mycobacterium tuberculosis lineages P˃0.05. However, rs17235409 was classified as marginal significant P=0.0570. Our study demonstrated that lineage 4 is the most predominant causing tuberculosis in Uganda followed by lineage 3 and Solute Carrier family 11A1 is implicated as a susceptibility gene for tuberculosis amongst the Ugandans and the association between M. tuberculosis and the human host is due to the genetic interaction of the two species in coexistence.