Genetic association of missense (rs2919643), intergenic (rs2057178) and a 3’UTR (rs1009170) variant with tuberculosis: A replication study from India

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution Pub Date : 2024-11-14 DOI:10.1016/j.meegid.2024.105690

Anuradha Gautam, Ahana Dasgupta , Suvamita Rout , Samsiddhi Bhattacharjee, Bhaswati Pandit

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引用次数: 0

Abstract

To investigate host genetic susceptibility to tuberculosis (TB), we conducted a replication study focussed on candidate SNPs, previously reported to be associated with TB. We examined nine candidate SNPs and genotyped them in an independent cohort of TB cases and household contacts from West Bengal, India. The association with TB was replicated for rs2919643 (Chr 18), rs2057178 (Chr 11) and rs1009170 (Chr 14). rs2919643-C (p=8.81E-5) was a risk allele and rs2057178-A (p=0.04188) was protective against TB in our population. Association of rs1009170; previously reported by us with TB was also replicated in the new set of samples (p=0.0359). rs2919643 is a missense variant present in linkage disequilibrium with a TB associated synonymous SNP rs61104666. The risk genotype rs2919643-CC was associated with higher levels of plasma RANTES and IL5 in household contacts. rs2919643 is an eQTL for an immunosuppressive gene SIGLEC15 and autophagy related gene EPG5. rs2057178 is an eQTL for a pseudogene and present within weak enhancer marks in the lungs. The genomic locus around this SNP rs1009170 encompasses an active transcription factor peak in CD14⁺ monocytes and also serves as an eQTL for NDUFB1, ATXN3 and SLC24A4. TB cases with rs1009170-TT genotype showed lower expression of plasma RANTES compared to the heterozygote. All three associated SNPs have putative regulatory role in lungs and immune associated cells and organs which may be relevant to TB pathogenesis.

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错义（rs2919643）、基因间（rs2057178）和 3'UTR （rs1009170）变异与结核病的遗传关联：印度的一项重复研究。

为了研究宿主对肺结核（TB）的遗传易感性，我们进行了一项复制研究，重点是以前报道过的与肺结核相关的候选 SNPs。我们研究了九个候选 SNPs，并在印度西孟加拉邦的结核病病例和家庭接触者的独立队列中对它们进行了基因分型。在我们的人群中，rs2919643-C（p = 8.81E-5）是风险等位基因，rs2057178-A（p = 0.04188）对结核病有保护作用。rs2919643 是一个错义变异，与结核病相关的同义 SNP rs61104666 存在连锁不平衡。rs2919643 是免疫抑制基因 SIGLEC15 和自噬相关基因 EPG5 的 eQTL。rs2057178 是假基因的 eQTL，存在于肺部的弱增强子标记中。围绕该 SNP rs1009170 的基因组位点包括 CD14+ 单核细胞中的一个活跃转录因子峰，同时也是 NDUFB1、ATXN3 和 SLC24A4 的 eQTL。与杂合子相比，rs1009170-TT 基因型的肺结核病例血浆 RANTES 表达较低。这三个相关的 SNPs 在肺部和免疫相关细胞及器官中都具有潜在的调节作用，可能与结核病的发病机制有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection Genetics and Evolution 医学-传染病学

CiteScore

8.40

自引率

0.00%

发文量

215

审稿时长

82 days

期刊介绍： (aka Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases -- MEEGID) Infectious diseases constitute one of the main challenges to medical science in the coming century. The impressive development of molecular megatechnologies and of bioinformatics have greatly increased our knowledge of the evolution, transmission and pathogenicity of infectious diseases. Research has shown that host susceptibility to many infectious diseases has a genetic basis. Furthermore, much is now known on the molecular epidemiology, evolution and virulence of pathogenic agents, as well as their resistance to drugs, vaccines, and antibiotics. Equally, research on the genetics of disease vectors has greatly improved our understanding of their systematics, has increased our capacity to identify target populations for control or intervention, and has provided detailed information on the mechanisms of insecticide resistance. However, the genetics and evolutionary biology of hosts, pathogens and vectors have tended to develop as three separate fields of research. This artificial compartmentalisation is of concern due to our growing appreciation of the strong co-evolutionary interactions among hosts, pathogens and vectors. Infection, Genetics and Evolution and its companion congress [MEEGID](http://www.meegidconference.com/) (for Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases) are the main forum acting for the cross-fertilization between evolutionary science and biomedical research on infectious diseases. Infection, Genetics and Evolution is the only journal that welcomes articles dealing with the genetics and evolutionary biology of hosts, pathogens and vectors, and coevolution processes among them in relation to infection and disease manifestation. All infectious models enter the scope of the journal, including pathogens of humans, animals and plants, either parasites, fungi, bacteria, viruses or prions. The journal welcomes articles dealing with genetics, population genetics, genomics, postgenomics, gene expression, evolutionary biology, population dynamics, mathematical modeling and bioinformatics. We also provide many author benefits, such as free PDFs, a liberal copyright policy, special discounts on Elsevier publications and much more. Please click here for more information on our author services .