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

IF 1.1 Q4 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

Global Health Epidemiology and Genomics Pub Date : 2018-01-23 eCollection Date: 2018-01-01 DOI:10.1017/gheg.2017.17

E Mekonnen, E Bekele, C M Stein

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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.

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埃塞俄比亚人群中与结核病进展表型相关的TICAM2和NOD1新多态性

背景:结核分枝杆菌(Mtb)感染是结核病(TB)的必要但不充分原因。尽管大量研究表明人类遗传变异可能影响结核病的发病机制，但明显缺乏复制，可能是由于表型定义不精确。我们的目的是在埃塞俄比亚人群中复制乌干达队列的新发现。方法:对来自3个不同民族的结核病例和家庭对照(n = 292)进行调查。使用Quantiferon测定潜伏结核感染，以建立可靠的结核进展表型。我们对TICAM2和NOD1的外显子区域进行了测序。结果:在NOD1和TB两种变异之间观察到显著的新关联:rs751770147[未经调整p = 7.28 × 10-5]和chr7:30477156(T)，一种新的变异，[未经调整p = 1.04 × 10-4]。名义上，TICAM2中的两个snp与TB相关，包括rs2288384[未经调整p = 0.003]。基于单倍型的关联测试支持基于snp的结果。结论:我们复制了TICAM2和NOD1与结核病的关联，并在埃塞俄比亚人群中发现了新的与结核病的遗传关联。

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