Missense variant rs75603675 within TMPRSS2 gene is associated with the increased risk of severe form of COVID-19

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2024-09-18 DOI:10.1016/j.genrep.2024.102039

Abdullah Al Saba , Jasmin Nur , Md Sohrab Alam , Zakir Hossain Howlader , Laila N. Islam , A.H.M. Nurun Nabi

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引用次数: 0

Abstract

Host genetics among other factors play an important role in COVID-19 disease severity. TMPRSS2, a serine protease, facilitates the priming of the SARS-CoV-2 spike protein, which is essential for the virus to enter the host cell. Several studies had targeted the TMPRSS2 polymorphisms with respect to SARS-CoV-2 infection and COVID-19 disease severity. Initially, the Whole Exome Sequencing (WES) of 7 healthy individuals and 22 COVID-19 patients with different degrees of disease severity was conducted to find the mutational landscape in different genes. A total of 26 single nucleotide polymorphisms (SNPs) were identified of which six were within the exons of TMPRSS2 (four synonymous and two nonsynonymous variants) while the rest of the 20 SNPs were recognized within the flanking intronic regions of TMPRSS2 gene. The nonsynonymous SNPs, rs75603675 and rs12329760, were further evaluated for association with disease severity in a larger sample size of 120 individuals by PCR followed by Sanger sequencing. Neither allelic nor genotypic distributions of rs12329760 were significantly associated with COVID-19 disease severity. However, individuals harboring the A allele of rs75603675 was found to have higher risk of severe COVID-19 compared to the C allele [OR (95%CI): 1.95 (1.11–3.39), p = 0.019]. Also, the genotype A/A [OR (95%CI): 5.13 (1.00–26.38), p = 0.033] of rs75603675 was associated with increased risk of severe COVID-19 under the recessive genetic inheritance model. Although the impact of COVID-19 pandemic has waned due to vaccination and public health measures, continued research on the association of COVID-19 disease severity and infection susceptibility with host genetics is required to shed valuable insights on the future long-term health effects of COVID-19 and impact of new variants on different populations and enable implication of proper informed healthcare strategies during future public health crises.

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TMPRSS2 基因中的错义变异 rs75603675 与 COVID-19 重症型风险增加有关

宿主遗传等因素对 COVID-19 疾病的严重程度起着重要作用。TMPRSS2是一种丝氨酸蛋白酶，能促进SARS-CoV-2尖峰蛋白的启动，而尖峰蛋白是病毒进入宿主细胞的必要条件。有几项研究针对 TMPRSS2 多态性与 SARS-CoV-2 感染和 COVID-19 疾病严重程度的关系进行了研究。最初，研究人员对 7 名健康人和 22 名病情严重程度不同的 COVID-19 患者进行了全外显子组测序（WES），以发现不同基因的突变情况。共鉴定出 26 个单核苷酸多态性（SNPs），其中 6 个在 TMPRSS2 的外显子中（4 个同义变异和 2 个非同义变异），其余 20 个 SNPs 在 TMPRSS2 基因的侧翼内含子区。非同义 SNPs（rs75603675 和 rs12329760）通过 PCR 和 Sanger 测序在 120 人的更大样本中进一步评估了与疾病严重程度的关联性。rs12329760的等位基因和基因型分布均与COVID-19疾病的严重程度无明显关联。然而，与 C 等位基因相比，携带 rs75603675 的 A 等位基因的个体罹患严重 COVID-19 的风险更高[OR (95%CI)：1.95 (1.11-3.39)，p = 0.019]。此外，在隐性遗传模式下，rs75603675 的基因型 A/A [OR (95%CI)：5.13 (1.00-26.38)，p = 0.033] 与严重 COVID-19 的风险增加有关。尽管由于疫苗接种和公共卫生措施的实施，COVID-19 大流行的影响已经减弱，但仍需继续研究 COVID-19 疾病严重程度和感染易感性与宿主遗传学的关联，以深入了解 COVID-19 对未来健康的长期影响以及新变异对不同人群的影响，并在未来公共卫生危机期间制定适当的知情医疗保健策略。

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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.