Patient Single Nucleotide Polymorphisms associated with Mycobacterium tuberculosis genotypes in the Ugandan population
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Objective: Despite strides in reducing the overall burden of tuberculosis, Uganda grapples with the enduring presence of three dominant Mycobacterium tuberculosis genotypes namely, Uganda family, lineage 3, and lineage 4. The persistence of the Mycobacterium tuberculosis Uganda genotype over the past two decades intrigues researchers because the underlying factors driving its prevalence remain enigmatic. While previous investigations have emphasized the role of host genetic factors in tuberculosis susceptibility, the specific mechanisms governing the uneven distribution of Mycobacterium tuberculosis lineages, notably the Uganda genotype, remain elusive. This study delved into the intricate landscape of Mycobacterium tuberculosis complex lineages and sub-lineages, coupled with the analysis of host Single Nucleotide Polymorphisms associated with specific Mycobacterium tuberculosis complex lineages. Results: The study scrutinized a total of 70 isolates, which revealed that the lineage 4 Uganda genotype constituted 50%, lineage 3 genotype 36%, while 4% comprised other lineage 4 strains, with 10% exhibiting mixed lineages. Despite rigorous analysis, no significant association was found between the examined Single Nucleotide Polymorphisms and Mycobacterium tuberculosis lineages , although rs17235409 showed marginal significance (P=0.0570). Our findings emphasize lineage 4 as the primary cause of tuberculosis in Uganda while implicating the Solute Carrier family 11A1 as the susceptibility gene among Ugandans.