Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations.
Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations.
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DOI：
10.1017/gheg.2017.17
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Stein CM
中科院分区：
文献类型：
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作者：
Mekonnen E;Bekele E;Stein CM
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。我们确定了来自三个不同种族的结核病病例和家庭对照（n = 292）。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。在NOD1和TB的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。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与结核病的新的遗传关联。
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.