Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: Evidence for coevolution?

• DOI: 10.1371/journal.pgen.1008728
• Publication Date: 2020-04-30T18:12:58Z
• Authors: Michael L. McHenry; Jacquelaine Bartlett; Robert P. Igo; Eddie M. Wampande; Penelope Benchek; Harriet Mayanja-K...; Kyle Fluegge; Noemi B. Hall; Sebastien Gagneux; Sarah A. Tishkoff; Christian Wejse; Giorgio Sirugo; W. Henry Boom; Moses Joloba; Scott M. Williams; Catherine M. Stein
• Keywords: SNP; Lineage (genetic); Genome-wide Association Study; Genetic Association; Coevolution

Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with (TB) risk. However, neither explains a large portion disease risk or severity. Based on in other infectious diseases animal models TB, we hypothesized that genomes two interact to modulate developing active TB increasing severity disease, when present. We examined this hypothesis our household contact study Kampala, Uganda, which there were 3 MTB lineages L4-Ugandan (L4.6) is most recent. severity, measured using Bandim TBscore, was modeled as function SNP genotype, lineage, their interaction, within cohorts cases, N = 113 121. No found between lineage but multiple polymorphisms IL12B TBscore replicated (most significant rs3212227, combined p 0.0006), supporting previous associations susceptibility. also observed interaction single nucleotide polymorphism (SNP) SLC11A1 (rs17235409, meta 0.0002). Interestingly, presence L4-Uganda ancestral allele associated more severe disease. These findings addition susceptibility, genetics can be due an genes species, consistent host-pathogen coevolution TB.