丝氨酸蛋白酶在SARS-CoV-2感染中起关键作用。因此,跨膜蛋白酶丝氨酸2(TMPRSS2)和serpine家族E成员1(SERPINE1)的多态性可能有助于阐明变异性对COVID-19结局的贡献。
为了评估先前与COVID-19结果相关的基因的遗传变异,我们进行了一项横断面研究,纳入了1536例SARS-CoV-2阳性参与者.使用开放式阵列平台对TMPRSS2(rs2070788、rs75603675、rs12329760)和SERPINE1(rs2227631、rs2227667、rs2070682、rs2227692)进行基因分型。多态性与疾病结局的关联是通过对协变量进行校正的逻辑回归分析确定的(年龄,性别,高血压,2型糖尿病,和肥胖)。
根据我们的共显性模型,Rs2227667的GA基因型(OR=0.55;95%CI=0.36-0.84;p=0.006)和Rs2227667的AG基因型(OR=0.59;95%CI=0.38-0.91;p=0.02)对疾病具有保护作用.然而,rs2227692T等位基因和TT基因型SERPINE1(OR=1.45;95%CI=1.11~1.91;p=0.006;OR=2.08;95%CI=1.22~3.57;p=0.007)与死亡风险降低相关.同样,对于死亡患者,rs75603675AA基因型TMPRSS2的OR为1.97(95%CI=1.07~3.6;p=0.03).最后,rs2227692T等位基因SERPINE1与D-二聚体水平升高相关(OR=1.24;95%CI=1.03-1.48;p=0.02).
我们的数据表明rs75603675TMPRSS2和rs2227692SERPINE1多态性与不良预后相关。此外,rs2227692SERPINE1可能参与重症COVID-19患者的高凝状态,这种遗传变异可能有助于确定新的药理靶标和治疗策略,以阻断TMPRSS2进入SARS-CoV-2的抑制作用。
Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (
SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.
To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and
SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity).
According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele
SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02).
Our data suggest that the rs75603675 TMPRSS2 and rs2227692
SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692
SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.