Polymorphisms within the SARS-CoV-2 Human Receptor Genes Associate with Variable Disease Outcomes across Ethnicities.
Polymorphisms within the SARS-CoV-2 Human Receptor Genes Associate with Variable Disease Outcomes across Ethnicities.
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DOI：
10.3390/genes14091798
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发表时间：
2023-09-14
期刊：
影响因子：
3.5
通讯作者：
Ramsuran, Veron
中科院分区：
文献类型：
--
作者：
Adimulam, Theolan;Arumugam, Thilona;Naidoo, Anushka;Naidoo, Kogieleum;Ramsuran, Veron
人类基因对疾病结果变异性的贡献已被证明在传染病中很重要。研究表明，特定人类基因内的突变与可变的COVID-19结果相关。我们专注于SARS-CoV-2受体/辅助受体，以确定ACE 2，TMPRSS 2，NRP 1和CD 147中特定多态性的作用。ACE 2（rs 2285666）、TMPRSS 2（rs 12329760）、CD 147（rs 8259）和NRP 1（rs 10080）内的多态性已被证明与COVID-19的严重程度相关。使用来自南非境内COVID-19阳性非洲人、欧洲人和南亚人的冷冻保存样本，我们确定了基因型频率。遗传变异rs 2285666与COVID-19严重程度相关，但存在种族偏见。与TT基因型相比，CC基因型的非洲个体表现出更严重的COVID-19结局（OR = 7.5; 95% CI 1.164-80.89; p = 0.024）。采用液滴数字PCR法检测ACE 2和SARS-CoV-2病毒载量的表达。我们的研究结果表明，rs 2285666和rs 10080在某些种族中与SARS-CoV-2病毒载量增加和预后不良显著相关。这项研究表明了两个重要的发现。首先，非洲人的SARS-CoV-2病毒载量明显低于欧洲人和南亚人后裔（p = 0.0002和p < 0.0001）。其次，SARS-CoV-2病毒载量与特异性SARS-CoV-2受体变异体相关。少数研究检查了非洲境内的受体/共受体基因。本研究调查了SARS-CoV-2受体/共受体基因内的遗传变异及其与不同种族COVID-19严重程度和SARS-CoV-2病毒载量的相关性。我们为南非不同种族群体之间COVID-19严重程度的差异提供了遗传基础，进一步强调了进一步调查的重要性，以确定潜在的治疗靶点，并指导可能优先考虑特定基因型的疫苗接种策略。
The contribution of human genes to the variability of disease outcomes has been shown to be important across infectious diseases. Studies have shown mutations within specific human genes are associated with variable COVID-19 outcomes. We focused on the SARS-CoV-2 receptors/co-receptors to identify the role of specific polymorphisms within ACE2, TMPRSS2, NRP1 and CD147. Polymorphisms within ACE2 (rs2285666), TMPRSS2 (rs12329760), CD147 (rs8259) and NRP1 (rs10080) have been shown to associate with COVID-19 severity. Using cryopreserved samples from COVID-19-positive African, European and South Asian individuals within South Africa, we determined genotype frequencies. The genetic variant rs2285666 was associated with COVID-19 severity with an ethnic bias. African individuals with a CC genotype demonstrate more severe COVID-19 outcomes (OR = 7.5; 95% CI 1.164–80.89; p = 0.024) compared with those with a TT genotype. The expressions of ACE2 and SARS-CoV-2 viral load were measured using droplet digital PCR. Our results demonstrate rs2285666 and rs10080 were significantly associated with increased SARS-CoV-2 viral load and worse outcomes in certain ethnicities. This study demonstrates two important findings. Firstly, SARS-CoV-2 viral load is significantly lower in Africans compared with individuals of European and South Asian descent (p = 0.0002 and p < 0.0001). Secondly, SARS-CoV-2 viral load associates with specific SARS-CoV-2 receptor variants. A limited number of studies have examined the receptor/co-receptor genes within Africa. This study investigated genetic variants within the SARS-CoV-2 receptor/co-receptor genes and their association with COVID-19 severity and SARS-CoV-2 viral load across different ethnicities. We provide a genetic basis for differences in COVID-19 severity across ethnic groups in South Africa, further highlighting the importance of further investigation to determine potential therapeutic targets and to guide vaccination strategies that may prioritize specific genotypes.
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DOI：
10.23750/abm.v94i1.13543
发表时间：
2023-02-13
期刊：
Acta bio-medica : Atenei Parmensis
影响因子：
--
作者：
通讯作者：
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DOI：
10.1186/s10020-021-00423-y
发表时间：
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期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
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作者：
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通讯作者：
Keegan AD
DOI：
10.1038/s41431-022-01058-1
发表时间：
2022-08
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Bruce J;Johnson SB
通讯作者：
Johnson SB
影响因子：
4.5
作者：
Anastassopoulou C;Gkizarioti Z;Patrinos GP;Tsakris A
通讯作者：
Tsakris A
影响因子：
9.3
作者：
Hou, Yuan;Zhao, Junfei;Cheng, Feixiong
通讯作者：
Cheng, Feixiong