The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy

Genes

Giuseppe Fiorentino¹  Pasquale Abete²  Gian Marco Cassese²  Ivan Gentile³  Roberta Marra⁴  Mario Capasso⁴  Vito Alessandro Lasorsa⁴  Gabriella Esposito⁴  Giulia Frisso⁴  Massimo Zollo⁴  Roberta Russo⁴  Immacolata Andolfo⁴  Achille Iolascon⁴  Sueva Cantalupo⁴  Giuseppe Servillo⁵  Pellegrino Cerino⁶  Carlo Buonerba⁶  Biancamaria Pierri⁶  Carmelo Piscopo⁷  Matteo Della Monica⁷  Giuseppe Russo⁸ 

[1] AORN dei Colli Presidio Ospedaliero Cotugno, 80131 Napoli, Italy;COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, 80042 Boscotrecase, Italy;Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy;Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy;Dipartimento di Neuroscienze e Scienze riproduttive ed odontostomatologiche, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy;Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy;Medical and Laboratory Genetics Unit, A.O.R.N. ‘Antonio Cardarelli’, 80131 Napoli, Italy;Unità di Radiologia, Casa di Cura Villa dei Fiori, 80011 Acerra, Italy;

关键词: COVID-19;    SARS-CoV-2;    whole-exome sequencing;    SNP genotyping;    CVID;    TNFRSF13C;   

DOI  :  10.3390/genes12060881

来源: DOAJ

【 摘 要 】

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.

【 授权许可】

Unknown