Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.
Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.
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DOI：
10.23750/abm.v94i1.13543
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发表时间：
2023-02-13
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编码宿主蛋白酶的基因多态性与病毒进入细胞有关，可以影响冠状病毒病19 （COVID-19）的易感性和死亡率。血管紧张素转换酶2 （ACE2）、跨膜丝氨酸2和丝氨酸11A蛋白酶（TMPRSS2、TMPRSS11A）和细胞表面分化簇147 （CD147）可能是产生这种影响的候选基因。本研究的目的是调查ace2、tmprss2、tmprss11a和cd147多态性变异与乌克兰人群中COVID-19严重程度之间的关系。研究人群包括乌克兰的COVID-19患者：未接受氧疗（n=62）、接受无创氧疗（n=92）和有创氧疗（n=35）的患者，以及对照组（n=92）。实时荧光定量PCR检测ace2 rs4240157、tmprss2 rs12329760、tmprss11a rs353163等位基因多态性，PCR检测cd147 rs8259等位基因多态性，并进行限制性酶分析。我们通过荟萃分析比较了调查的多态性分布与其他人群。我们的研究首次获得了乌克兰人群中所调查基因多态性的分布数据：tmprss2 rs12329760 - CC 60.9%, CT 35.9%, TT 3.2%；tmprss11a rs353163 - CC 46.7%, CT 40.2%, TT 13.1%；ace2 rs4240157 - CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%；cd147 rs8259 - TT 60.9%, AT 32.6%, AA 6.5%。这种分布与北欧、西欧和南欧人口相似。有创氧疗组与无创氧疗组相比，tmprss2基因型多态性频率CC 57.1%、CT 28.6%、TT 14.3%差异有统计学意义（P<0.05）。这种tmprss2突变发生在富含半胱氨酸的清除率受体（SRCR）结构域，可能对钙依赖方式下的蛋白-蛋白相互作用很重要。我们的研究表明，乌克兰人群中tmprss2 rs12329760多态性与COVID-19严重程度之间存在关联。(）
Gene polymorphism, coding the host proteases, which are involved in the virus entry into the cells can influence the susceptibility to and mortality from coronavirus disease 19 (COVID-19). Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that exerts such influence. The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population. The study population consisted of the Ukrainian population with COVID-19: patients without oxygen therapy (n=62), with non-invasive (n=92) and invasive (n=35) oxygen therapy, as well as control subjects (n=92). Allelic polymorphisms of ace2 rs4240157, tmprss2 rs12329760, and tmprss11a rs353163 were determined by real-time PCR, and cd147 rs8259 polymorphism was detected by PCR with subsequent restrictase analysis. We compared investigated polymorphisms distribution with other populations by meta-analysis. Our study is the first to obtain data about the distribution of investigated gene polymorphisms in the Ukrainian population: tmprss2 rs12329760 – CC 60.9%, CT 35.9%, TT 3.2%; tmprss11a rs353163 – CC 46.7%, CT 40.2%, TT 13.1%; ace2 rs4240157 – CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%; cd147 rs8259 – TT 60.9%, AT 32.6%, AA 6.5%. This distribution was similar to the Northern, Western and Southern European populations. There was a statistically significant difference in the frequency of tmprss2 polymorphic genotypes CC 57.1%, CT 28.6%, and TT 14.3% (P<0.05) in COVID-19 patients with invasive oxygen therapy in comparison with non-invasive oxygen therapy. This tmprss2 mutation occurs in the scavenger receptor cysteine-rich (SRCR) domain and might be important for protein-protein interaction in a calcium-dependent manner. Our study indicated the presence of an association between the tmprss2 rs12329760 polymorphism and the severity of COVID-19 in the Ukrainian population. ()