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

E Mekonnen,C M Stein,E Bekele

doi:10.1017/gheg.2017.17

Abstract

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.

Highlights

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health threat globally
We replicated the association of TICAM2 and NOD1 with TB and identified novel genetic associations with TB in Ethiopian populations
TB pathogenesis follows a two-stage process: first, uninfected individuals become exposed to infectious TB cases, and may progress to Mtb infection, though not all subjects exposed to TB become infected [1]

Summary

Introduction

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health threat globally. It is estimated that one-third of the world is infected with Mtb, and roughly. 10% of these individuals progress to active TB disease. TB pathogenesis follows a two-stage process: first, uninfected individuals become exposed to infectious TB cases, and may progress to Mtb infection, though not all subjects exposed to TB become infected [1]. In the second stage, ∼10% of Mtb-infected individuals progress to active TB disease. These two stages may have different genetic underpinnings. In 2014, the estimated prevalence of TB in Ethiopia was 200 per 100 000 and incidence of 207 per 100 000 [2]. Infection by Mycobacterium tuberculosis (Mtb) is a necessary but not sufficient cause for tuberculosis (TB). We aimed to replicate novel findings from a Ugandan cohort in Ethiopian populations

Objectives

Methods

Results

Conclusion