PDF(Pubmed)
Abstract：
Genes involved in the regulation of viral recognition and its entry into a host cell have been identified as candidates for genetic association studies on COVID-19 severity. Published findings on the effects of polymorphisms within ACE1, ACE2, TMPRSS2, IFITM3 and VDR genes remained inconclusive, so we conducted a systematic review and meta-analysis in order to elucidate their potential involvement in the genetic basis underlying the severity of COVID-19 and/or an outcome of SARS-CoV-2 infection. Identification of potentially eligible studies was based on PubMed, Scopus and Web of Science database search. Relevant studies (n=29) with a total number of 8247 SARS-CoV-2-positive participants were included in qualitative synthesis, while results of 21 studies involving 5939 were pooled in meta-analysis. Minor allele I of rs1799752 located within ACE1 was identified as a protective variant against severe COVID-19, while its effect on mortality rate was opposite. Similarly, minor allele A of ACE2 polymorphism, rs2285666, was found to associate with a decreased risk of severe COVID-19 (P = 0.003, OR = 0.512, 95 % CI = 0.331-0.793). Statistical significance was also seen for the association between COVID-19 severity and rs12329760 located within TMPRSS2. Our results did not support the supposed association of rs12252 in IFITM3 and polymorphisms within VDR with disease severity. We conclude that genetic variants within ACE1, ACE2 and TMPRSS2 may be potential biomarkers of COVID-19 severity, which needs to be further confirmed in a larger set of studies.
摘要：
参与调节病毒识别及其进入宿主细胞的基因已被确定为关于COVID-19严重程度的遗传关联研究的候选基因。发表的关于ACE1，ACE2，TMPRSS2，IFITM3和VDR基因多态性影响的研究结果仍然没有定论，因此,我们进行了系统评价和荟萃分析,以阐明它们可能参与COVID-19严重程度和/或SARS-CoV-2感染结局的遗传基础.潜在合格研究的确定是基于PubMed，Scopus和WebofScience数据库搜索。相关研究（n=29），共有8247名SARS-CoV-2阳性参与者被纳入定性综合，而21项涉及5939项研究的结果纳入荟萃分析.位于ACE1内的rs1799752的次要等位基因I被鉴定为针对严重COVID-19的保护性变体，而其对死亡率的影响则相反。同样，ACE2多态性的次要等位基因A，rs2285666与严重COVID-19的风险降低相关(P=0.003，OR=0.512，95%CI=0.331-0.793)。COVID-19严重程度与位于TMPRSS2内的rs12329760之间的关联也有统计学意义。我们的结果不支持IFITM3中rs12252和VDR内多态性与疾病严重程度的假设关联。我们得出结论，ACE1，ACE2和TMPRSS2内的遗传变异可能是COVID-19严重程度的潜在生物标志物，这需要在更大的研究中进一步证实。
