Functional associations between polymorphic regions of the human 3'IgH locus and COVID-19 disease
Copyright © 2022 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:838 |
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| Enthalten in: |
Gene - 838(2022) vom: 05. Sept., Seite 146698 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Colucci, Mattia [VerfasserIn] |
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| Links: |
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| Themen: |
Allelic polymorphisms |
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| Anmerkungen: |
Date Completed 26.07.2022 Date Revised 26.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.gene.2022.146698 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM342934821 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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