ACE2、TMPRSS2、TYK2、SLC6A20和IFNAR2基因变异对SARS-CoV-2感染易感性的影响

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-04-15 DOI:10.1016/j.genrep.2025.102228

Seyedeh Sepideh Aghamirli , Mohammad Zarif , Marzieh Khalouei , Kolsoum Saeidi , Nasrollah Saleh-Gohari

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引用次数: 0

摘要

本横断面研究探讨了影响2019冠状病毒病（COVID-19）易感性的遗传因素，重点研究了血管紧张素转换酶2 （ACE2）、跨膜丝氨酸蛋白酶2 （TMPRSS2）、酪氨酸激酶2 （TYK2）、溶质载体家族6成员20 （SLC6A20）和干扰素α和β受体亚基2 （IFNAR2）等关键人类基因的作用。对100名有或没有SARS-CoV-2感染史的个体进行了全外显子组测序。在这些基因中共鉴定出140种遗传变异，包括单核苷酸变异、插入/缺失和剪接变异。在这些变异中，ACE2中的rs75949720和rs776459296、TMPRSS2中的rs386818798和IFNAR2中的rs759744926等9个变异被发现增加了COVID-19的风险。为了进一步探索其影响，采用生物信息学同源建模来评估这些遗传变化如何影响相关蛋白的三维（3D）结构，揭示可能导致疾病严重程度的功能改变。这些发现表明，这些基因的变异可能在COVID-19的发病机制中发挥关键作用，突出了在开发靶向治疗和疫苗以更好地管理疾病时考虑遗传因素的重要性。

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Influence of the ACE2, TMPRSS2, TYK2, SLC6A20, and IFNAR2 gene variants on susceptibility to SARS-CoV-2 infection

This cross-sectional study investigates the genetic factors influencing susceptibility to coronavirus disease 2019 (COVID-19), focusing on the role of key human genes, including angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), tyrosine kinase 2 (TYK2), solute carrier family 6 member 20 (SLC6A20), and interferon alpha and beta receptor subunit 2 (IFNAR2). Whole-exome sequencing was performed on a cohort of 100 individuals, both with and without a history of SARS-CoV-2 infection. A total of 140 genetic variations, including single nucleotide variations, insertions/deletions, and splicing variants, were identified across these genes. Among the variants, nine, such as rs759499720 and rs776459296 in ACE2, rs386818798 in TMPRSS2, and rs759744926 in IFNAR2, were found to increase the risk of COVID-19. To further explore their impact, bioinformatics homology modeling was employed to assess how these genetic changes affect the three-dimensional (3D) structure of the associated proteins, revealing functional alterations that may contribute to disease severity. These findings suggest that variations in these genes may play a critical role in the pathogenesis of COVID-19, highlighting the importance of considering genetic factors in the development of targeted treatments and vaccines for better disease management.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.