Epistolio Samantha, Ramelli Giulia, Ottaviano Margaret, Crupi Emanuele, Marandino Laura, Biggiogero Maira, Maida Pier Andrea, Ruinelli Lorenzo, Vogl Ursula, Mangan Dylan, Pascale Mariarosa, Cantù Marco, Ceschi Alessandro, Bernasconi Enos, Mazzucchelli Luca, Catapano Carlo, Alimonti Andrea, Garzoni Christian, Gillessen Sommer Silke, Stefanini Federico Mattia, Franzetti-Pellanda Alessandra, Frattini Milo, Pereira Mestre Ricardo
Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale, Locarno, Switzerland.
Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
Front Med (Lausanne). 2022 Jul 7;8:793728. doi: 10.3389/fmed.2021.793728. eCollection 2021.
Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. This is the first study showing that gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）通过血管紧张素转换酶2（ACE2）受体和跨膜丝氨酸蛋白酶2（TMPRSS2）利用雄激素受体（AR）进入鼻腔和上呼吸道上皮细胞。基因分析显示，与P1245A变体相比，P1245C多态性变体增加了二氢睾酮的产生并上调了TMPRSS2，从而可能影响SARS-CoV-2感染。我们的目的是在瑞士南部住院的COVID-19患者中，对该多态性状态及其与临床结局的潜在关联进行特征分析。该队列包括2020年2月至5月第一波疫情期间在提契诺州两家不同医院因COVID-19住院的400名患者。从福尔马林固定石蜡包埋的组织块中提取基因组DNA，并通过桑格测序评估基因多态性。使用不同的检验方法验证统计关联。多态性变体与SARS-CoV-2住院患者中与较差临床预后相关的单一经典因素无关。然而，在特定亚组中，这些变体发挥了临床作用：与无此合并症的P1245A个体相比，P1245C糖尿病患者入住重症监护病房的可能性更大，与无高血压的P1245A糖尿病患者相比，高血压P1245A>C病例的死亡关联更大。这是第一项表明该基因状态可能影响SARS-CoV-2感染严重程度的研究。如果得到证实，我们的结果可能会导致对感染SARS-CoV-2的患者进行该基因状态分析，以预测临床结局。
