Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations. (23rd January 2018)

• Record Type: Journal Article
• Authors: Mekonnen, E.; Bekele, E.; Stein, C. M.
• Is Part Of: Global health, epidemiology and genomics. Volume 3(2018)
• Publication Date: 2018-01-23
• Subjects: Case-contact study, -- genetic epidemiology, -- human genetic polymorphism, -- innate immunity, -- latent tuberculosis infection, -- tuberculosis genetics; World health -- Periodicals; Genomics -- Periodicals; Medical policy -- Periodicals; Epidemiology -- Periodicals; Global Health; Epidemiology; Genomics; Periodicals; Periodicals; Electronic journals; 362.1
• DOI: 10.1017/gheg.2017.17
• Languages: English
• ISSNs: 2054-4200

Abstract

Abstract : 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.