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Published on: September 26, 2025
Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations
E Mekonnen1,2, E Bekele3, C M Stein4
1Microbial, Cellular, Molecular Biology Department, Addis Ababa University, P.O.Box:17087, Addis Ababa, Ethiopia.
Background:
Infection by Mycobacterium tuberculosis (Mtb) is a necessary but not sufficient cause for tuberculosis (TB). Although numerous studies suggest human genetic variation may influence TB pathogenesis, there is a conspicuous lack of replication, likely due to imprecise phenotype definition. We aimed to replicate novel findings from a Ugandan cohort in Ethiopian populations.
Method:
We ascertained TB cases and household controls (n = 292) from three different ethnic groups. Latent Mtb infection was determined using Quantiferon to develop reliable TB progression phenotypes. We sequenced exonic regions of TICAM2 and NOD1.
Result:
Significant novel associations were observed between two variants in NOD1 and TB: rs751770147 [unadjusted p = 7.28 × 10-5] and chr7:30477156(T), a novel variant, [unadjusted p = 1.04 × 10-4]. Two SNPs in TICAM2 were nominally associated with TB, including rs2288384 [unadjusted p = 0.003]. Haplotype-based association tests supported the SNP-based results.
Conclusion:
We replicated the association of TICAM2 and NOD1 with TB and identified novel genetic associations with TB in Ethiopian populations.
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The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...

