Mózner Orsolya, Szabó Edit, Kulin Anna, Várady György, Moldvay Judit, Vass Vivien, Szentesi Andrea, Jánosi Ágoston, Hegyi Péter, Sarkadi Balázs
Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Doctoral School, Semmelweis University, Budapest, Hungary.
PLoS One. 2025 Jan 3;20(1):e0316396. doi: 10.1371/journal.pone.0316396. eCollection 2025.
In this study, we analyzed the potential associations of selected laboratory and anamnestic parameters, as well as 12 genetic polymorphisms (SNPs), with clinical COVID-19 occurrence and severity in 869 hospitalized patients. The SNPs analyzed by qPCR were selected based on population-wide genetic (GWAS) data previously indicating association with the severity of COVID-19, and additional SNPs that have been shown to be important in cellular processes were also examined. We confirmed the associations of COVID-19 with pre-existing diabetes and found an unexpected association between less severe disease and the loss of smell and taste. Regarding the genetic polymorphisms, a higher allele frequency of the LZTFL1 and IFNAR2 minor variants significantly correlated with greater COVID-19 disease susceptibility (hospitalization) and severity, and a similar tendency was observed for the RAVER1 and the MUC5B variants. Interestingly, the ATP2B4 minor haplotype, protecting against malaria, correlated with an increased disease susceptibility, while in diabetic patients disease susceptibility was lower in the presence of a reduced-function ABCG2 transporter variant. Our current results, which should be reinforced by larger studies, indicate that together with laboratory and anamnestic parameters, genetic polymorphisms may have predictive value for the clinical occurrence and severity of COVID-19.
在本研究中，我们分析了869例住院患者中选定的实验室和既往病史参数以及12种基因多态性（单核苷酸多态性，SNPs）与临床COVID-19发生及严重程度之间的潜在关联。通过定量聚合酶链反应（qPCR）分析的SNPs是根据此前表明与COVID-19严重程度相关的全人群基因（全基因组关联研究，GWAS）数据选定的，还检测了在细胞过程中已显示重要作用的其他SNPs。我们证实了COVID-19与既往糖尿病之间的关联，并发现病情较轻与嗅觉和味觉丧失之间存在意外关联。关于基因多态性，LZTFL1和IFNAR2次要变体的较高等位基因频率与更高的COVID-19疾病易感性（住院）和严重程度显著相关，RAVER1和MUC5B变体也观察到类似趋势。有趣的是，具有抗疟疾作用的ATP2B4次要单倍型与疾病易感性增加相关，而在糖尿病患者中，功能降低的ABCG2转运体变体存在时疾病易感性较低。我们目前的结果（应通过更大规模研究予以强化）表明，基因多态性与实验室和既往病史参数一起，可能对COVID-19的临床发生及严重程度具有预测价值。
