Cargando…
Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease
PURPOSE: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant gender-related differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. METHOD...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Published by Elsevier B.V.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241982/ https://www.ncbi.nlm.nih.gov/pubmed/35772651 http://dx.doi.org/10.1016/j.gene.2022.146698 |
_version_ | 1784737951670861824 |
---|---|
author | Colucci, Mattia Frezza, Domenico Gambassi, Giovanni De Vito, Francesco Iaquinta, Angela Grazia Massaro, Maria Di Giambenedetto, Simona Borghetti, Alberto Lombardi, Francesca Panzironi, Noemi Ruggieri, Valentino Giambra, Vincenzo Cianci, Rossella |
author_facet | Colucci, Mattia Frezza, Domenico Gambassi, Giovanni De Vito, Francesco Iaquinta, Angela Grazia Massaro, Maria Di Giambenedetto, Simona Borghetti, Alberto Lombardi, Francesca Panzironi, Noemi Ruggieri, Valentino Giambra, Vincenzo Cianci, Rossella |
author_sort | Colucci, Mattia |
collection | PubMed |
description | PURPOSE: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant gender-related differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. METHODS: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 ± 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3’Regulatory Region (3’RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. RESULTS: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ERα) in the polymorphic enhancer hs1.2 of 3’RR-1, was significantly enriched in women with a less severe disease. CONCLUSIONS: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans. |
format | Online Article Text |
id | pubmed-9241982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92419822022-06-30 Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease Colucci, Mattia Frezza, Domenico Gambassi, Giovanni De Vito, Francesco Iaquinta, Angela Grazia Massaro, Maria Di Giambenedetto, Simona Borghetti, Alberto Lombardi, Francesca Panzironi, Noemi Ruggieri, Valentino Giambra, Vincenzo Cianci, Rossella Gene Article PURPOSE: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant gender-related differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. METHODS: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 ± 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3’Regulatory Region (3’RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. RESULTS: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ERα) in the polymorphic enhancer hs1.2 of 3’RR-1, was significantly enriched in women with a less severe disease. CONCLUSIONS: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans. Published by Elsevier B.V. 2022-06-27 /pmc/articles/PMC9241982/ /pubmed/35772651 http://dx.doi.org/10.1016/j.gene.2022.146698 Text en © 2022 Published by Elsevier B.V. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Colucci, Mattia Frezza, Domenico Gambassi, Giovanni De Vito, Francesco Iaquinta, Angela Grazia Massaro, Maria Di Giambenedetto, Simona Borghetti, Alberto Lombardi, Francesca Panzironi, Noemi Ruggieri, Valentino Giambra, Vincenzo Cianci, Rossella Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease |
title | Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease |
title_full | Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease |
title_fullStr | Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease |
title_full_unstemmed | Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease |
title_short | Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease |
title_sort | functional associations between polymorphic regions of the human 3'igh locus and covid-19 disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241982/ https://www.ncbi.nlm.nih.gov/pubmed/35772651 http://dx.doi.org/10.1016/j.gene.2022.146698 |
work_keys_str_mv | AT coluccimattia functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT frezzadomenico functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT gambassigiovanni functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT devitofrancesco functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT iaquintaangela functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT graziamassaromaria functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT digiambenedettosimona functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT borghettialberto functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT lombardifrancesca functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT panzironinoemi functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT ruggierivalentino functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT giambravincenzo functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease AT ciancirossella functionalassociationsbetweenpolymorphicregionsofthehuman3ighlocusandcovid19disease |