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Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations

  • E. Mekonnen (a1) (a2), E. Bekele (a3) and C. M. Stein (a4)

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.


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.


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.


We replicated the association of TICAM2 and NOD1 with TB and identified novel genetic associations with TB in Ethiopian populations.

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This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
*Address for correspondence: E. Mekonnen, Microbial, Cellular, Molecular Biology Department, Addis Ababa University; Health Biotechnology Department, Institute of Biotechnology, Addis Ababa University, P.O.Box:17087, Addis Ababa, Ethiopia (Email:
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