The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population
Background: Diversity in response on exposure to severe acute respiratory syndrome coronavirus 2 may be related to the innate immune response in the elderly. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorph...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/74b3faf17a3a41a2bee1cbf580255bc2 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:74b3faf17a3a41a2bee1cbf580255bc2 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:74b3faf17a3a41a2bee1cbf580255bc22021-11-30T13:24:19ZThe MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population2296-858X10.3389/fmed.2021.668024https://doaj.org/article/74b3faf17a3a41a2bee1cbf580255bc22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.668024/fullhttps://doaj.org/toc/2296-858XBackground: Diversity in response on exposure to severe acute respiratory syndrome coronavirus 2 may be related to the innate immune response in the elderly. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele is a risk allele for the non-infectious aging lung disease idiopathic pulmonary fibrosis (IPF). We investigated if MUC5B rs35705950 associates with severe COVID-19.Methods: In this retrospective candidate gene case-control study we recruited 108 Dutch patients (69% male, median age 66 years, 77% white) requiring hospitalization for COVID-19 (22% ICU stay, 24% died). For validation, genotypes were obtained from the UK-Biobank (n = 436, 57% male, median age 70 years, 27% died), for replication data from the severe COVID-19 GWAS group from Italy (n = 835) and Spain (n = 775) was used, each with a control cohort (n = 356,735, n = 1,255, n = 950, respectively). MUC5B association analysis was performed including adjustment for age and sex.Results: The rs35705950 T-allele frequency was significantly lower in Dutch white patients (n = 83) than in controls (0.04 vs. 0.10; p = 0.02). This was validated in the UK biobank cohort (0.08 vs. 0.11; p = 0.001). While age and sex differed significantly between cases and control, comparable results were obtained with age and sex as confounding variables in a multivariate analysis. The association was replicated in the Italian (p = 0.04), and Spanish (p = 0.03) case-control cohorts. Meta-analysis showed a negative association for the T-allele with COVID-19 (OR = 0.75 (CI: 0.67–0.85); p = 6.63 × 10−6).Conclusions: This study shows that carriage of the T-allele of MUC5B rs35705950 confers protection from development of severe COVID-19. Because the T-allele is a known risk allele for IPF, this study provides further evidence for the existence of trade-offs between optimal mucin expression levels in the aging lung.Coline H. M. van MoorselColine H. M. van MoorselJoanne J. van der VisJoanne J. van der VisAnna DuckworthChris J. ScottonClaudia BenschopClaudia BenschopDavid EllinghausDavid EllinghausHenk J. T. RuvenMarian J. R. QuanjelJan C. GruttersJan C. GruttersFrontiers Media S.A.articleMUC5BCOVID-19idiopathic pulmonary fibrosisinnate immunitymucusSARS-CoV-2Medicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
MUC5B COVID-19 idiopathic pulmonary fibrosis innate immunity mucus SARS-CoV-2 Medicine (General) R5-920 |
| spellingShingle |
MUC5B COVID-19 idiopathic pulmonary fibrosis innate immunity mucus SARS-CoV-2 Medicine (General) R5-920 Coline H. M. van Moorsel Coline H. M. van Moorsel Joanne J. van der Vis Joanne J. van der Vis Anna Duckworth Chris J. Scotton Claudia Benschop Claudia Benschop David Ellinghaus David Ellinghaus Henk J. T. Ruven Marian J. R. Quanjel Jan C. Grutters Jan C. Grutters The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population |
| description |
Background: Diversity in response on exposure to severe acute respiratory syndrome coronavirus 2 may be related to the innate immune response in the elderly. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele is a risk allele for the non-infectious aging lung disease idiopathic pulmonary fibrosis (IPF). We investigated if MUC5B rs35705950 associates with severe COVID-19.Methods: In this retrospective candidate gene case-control study we recruited 108 Dutch patients (69% male, median age 66 years, 77% white) requiring hospitalization for COVID-19 (22% ICU stay, 24% died). For validation, genotypes were obtained from the UK-Biobank (n = 436, 57% male, median age 70 years, 27% died), for replication data from the severe COVID-19 GWAS group from Italy (n = 835) and Spain (n = 775) was used, each with a control cohort (n = 356,735, n = 1,255, n = 950, respectively). MUC5B association analysis was performed including adjustment for age and sex.Results: The rs35705950 T-allele frequency was significantly lower in Dutch white patients (n = 83) than in controls (0.04 vs. 0.10; p = 0.02). This was validated in the UK biobank cohort (0.08 vs. 0.11; p = 0.001). While age and sex differed significantly between cases and control, comparable results were obtained with age and sex as confounding variables in a multivariate analysis. The association was replicated in the Italian (p = 0.04), and Spanish (p = 0.03) case-control cohorts. Meta-analysis showed a negative association for the T-allele with COVID-19 (OR = 0.75 (CI: 0.67–0.85); p = 6.63 × 10−6).Conclusions: This study shows that carriage of the T-allele of MUC5B rs35705950 confers protection from development of severe COVID-19. Because the T-allele is a known risk allele for IPF, this study provides further evidence for the existence of trade-offs between optimal mucin expression levels in the aging lung. |
| format |
article |
| author |
Coline H. M. van Moorsel Coline H. M. van Moorsel Joanne J. van der Vis Joanne J. van der Vis Anna Duckworth Chris J. Scotton Claudia Benschop Claudia Benschop David Ellinghaus David Ellinghaus Henk J. T. Ruven Marian J. R. Quanjel Jan C. Grutters Jan C. Grutters |
| author_facet |
Coline H. M. van Moorsel Coline H. M. van Moorsel Joanne J. van der Vis Joanne J. van der Vis Anna Duckworth Chris J. Scotton Claudia Benschop Claudia Benschop David Ellinghaus David Ellinghaus Henk J. T. Ruven Marian J. R. Quanjel Jan C. Grutters Jan C. Grutters |
| author_sort |
Coline H. M. van Moorsel |
| title |
The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population |
| title_short |
The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population |
| title_full |
The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population |
| title_fullStr |
The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population |
| title_full_unstemmed |
The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population |
| title_sort |
muc5b promoter polymorphism associates with severe covid-19 in the european population |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/74b3faf17a3a41a2bee1cbf580255bc2 |
| work_keys_str_mv |
AT colinehmvanmoorsel themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT colinehmvanmoorsel themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT joannejvandervis themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT joannejvandervis themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT annaduckworth themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT chrisjscotton themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT claudiabenschop themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT claudiabenschop themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT davidellinghaus themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT davidellinghaus themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT henkjtruven themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT marianjrquanjel themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT jancgrutters themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT jancgrutters themuc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT colinehmvanmoorsel muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT colinehmvanmoorsel muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT joannejvandervis muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT joannejvandervis muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT annaduckworth muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT chrisjscotton muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT claudiabenschop muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT claudiabenschop muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT davidellinghaus muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT davidellinghaus muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT henkjtruven muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT marianjrquanjel muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT jancgrutters muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation AT jancgrutters muc5bpromoterpolymorphismassociateswithseverecovid19intheeuropeanpopulation |
| _version_ |
1718406570479452160 |