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.
The tnfrsf13c h159y variant is associated with severe covid-19: A retrospective study of 500 patients from southern italy / Russo, R.; Andolfo, I.; Lasorsa, V. A.; Cantalupo, S.; Marra, R.; Frisso, G.; Abete, P.; Cassese, G. M.; Servillo, G.; Esposito, G.; Gentile, I.; Piscopo, C.; Della Monica, M.; Fiorentino, G.; Russo, G.; Cerino, P.; Buonerba, C.; Pierri, B.; Zollo, M.; Iolascon, A.; Capasso, M.. - In: GENES. - ISSN 2073-4425. - 12:6(2021), p. 881. [10.3390/genes12060881]
The tnfrsf13c h159y variant is associated with severe covid-19: A retrospective study of 500 patients from southern italy
Russo R.;Andolfo I.;Lasorsa V. A.;Cantalupo S.;Frisso G.;Abete P.;Cassese G. M.;Servillo G.;Gentile I.;Cerino P.;Buonerba C.;Pierri B.;Zollo M.;Iolascon A.;Capasso M.
2021
Abstract
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.File | Dimensione | Formato | |
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