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Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19.
Cantalupo, Sueva; Lasorsa, Vito Alessandro; Russo, Roberta; Andolfo, Immacolata; D'Alterio, Giuseppe; Rosato, Barbara Eleni; Frisso, Giulia; Abete, Pasquale; Cassese, Gian Marco; Servillo, Giuseppe; Gentile, Ivan; Piscopo, Carmelo; Della Monica, Matteo; Fiorentino, Giuseppe; Russo, Giuseppe; Cerino, Pellegrino; Buonerba, Carlo; Pierri, Biancamaria; Zollo, Massimo; Iolascon, Achille; Capasso, Mario.
  • Cantalupo S; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80136 Napoli, Italy.
  • Lasorsa VA; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • Russo R; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80136 Napoli, Italy.
  • Andolfo I; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • D'Alterio G; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80136 Napoli, Italy.
  • Rosato BE; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • Frisso G; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80136 Napoli, Italy.
  • Abete P; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • Cassese GM; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • Servillo G; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80136 Napoli, Italy.
  • Gentile I; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • Piscopo C; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80136 Napoli, Italy.
  • Della Monica M; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
  • Fiorentino G; COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, 80042 Boscotrecase, Italy.
  • Russo G; COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, 80042 Boscotrecase, Italy.
  • Cerino P; Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy.
  • Buonerba C; Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy.
  • Pierri B; Medical and Laboratory Genetics Unit, A.O.R.N. 'Antonio Cardarelli', 80131 Napoli, Italy.
  • Zollo M; Medical and Laboratory Genetics Unit, A.O.R.N. 'Antonio Cardarelli', 80131 Napoli, Italy.
  • Iolascon A; AORN dei Colli Presidio Ospedaliero Cotugno, 80131 Napoli, Italy.
  • Capasso M; Unità di Radiologia, Casa di Cura Villa dei Fiori, 80011 Acerra, Italy.
Int J Mol Sci ; 22(10)2021 May 20.
Article in English | MEDLINE | ID: covidwho-1244036
Semantic information from SemMedBD (by NLM)
1. CCR5 gene|CCR5 PREDISPOSES COVID-19
Subject
CCR5 gene|CCR5
Predicate
PREDISPOSES
Object
COVID-19
2. CCR5 gene|CCR5 ASSOCIATED_WITH Communicable Diseases
Subject
CCR5 gene|CCR5
Predicate
ASSOCIATED_WITH
Object
Communicable Diseases
3. COVID-19 PROCESS_OF hospitalized patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
hospitalized patients
4. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
5. Structure of parenchyma of lung LOCATION_OF Alleles
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
Alleles
6. Single Nucleotide Polymorphism ASSOCIATED_WITH COVID-19
Subject
Single Nucleotide Polymorphism
Predicate
ASSOCIATED_WITH
Object
COVID-19
7. Binding Sites INTERACTS_WITH CCR5 gene|CCR5
Subject
Binding Sites
Predicate
INTERACTS_WITH
Object
CCR5 gene|CCR5
8. Structure of parenchyma of lung LOCATION_OF CCR5 gene|CCR5
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
CCR5 gene|CCR5
9. Binding Sites ASSOCIATED_WITH COVID-19
Subject
Binding Sites
Predicate
ASSOCIATED_WITH
Object
COVID-19
10. CCR5 gene|CCR5 PREDISPOSES COVID-19
Subject
CCR5 gene|CCR5
Predicate
PREDISPOSES
Object
COVID-19
11. CCR5 gene|CCR5 ASSOCIATED_WITH Communicable Diseases
Subject
CCR5 gene|CCR5
Predicate
ASSOCIATED_WITH
Object
Communicable Diseases
12. COVID-19 PROCESS_OF hospitalized patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
hospitalized patients
13. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
14. Structure of parenchyma of lung LOCATION_OF Alleles
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
Alleles
15. Single Nucleotide Polymorphism ASSOCIATED_WITH COVID-19
Subject
Single Nucleotide Polymorphism
Predicate
ASSOCIATED_WITH
Object
COVID-19
16. Binding Sites INTERACTS_WITH CCR5 gene|CCR5
Subject
Binding Sites
Predicate
INTERACTS_WITH
Object
CCR5 gene|CCR5
17. Structure of parenchyma of lung LOCATION_OF CCR5 gene|CCR5
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
CCR5 gene|CCR5
18. Binding Sites ASSOCIATED_WITH COVID-19
Subject
Binding Sites
Predicate
ASSOCIATED_WITH
Object
COVID-19
ABSTRACT
Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, CCR5 / Genetic Predisposition to Disease / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Prognostic study / Risk factors Topics: Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22105372

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, CCR5 / Genetic Predisposition to Disease / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Prognostic study / Risk factors Topics: Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22105372