Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality
Background: coronavirus disease 2019 (COVID-19) causes severe illness including cytokine storms, but mortality among countries differs largely. In the present study, we investigated the association between human leukocyte antigen (HLA) class I, which plays a major role in susceptibility to viral inf...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/11/1333 |
| _version_ | 1797547293290790912 |
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| author | Atsushi Sakuraba Haider Haider Toshiro Sato |
| author_facet | Atsushi Sakuraba Haider Haider Toshiro Sato |
| author_sort | Atsushi Sakuraba |
| collection | DOAJ |
| description | Background: coronavirus disease 2019 (COVID-19) causes severe illness including cytokine storms, but mortality among countries differs largely. In the present study, we investigated the association between human leukocyte antigen (HLA) class I, which plays a major role in susceptibility to viral infections, and the mortality of COVID-19. Methods: data of allele frequencies of HLA-A, -B and -C and COVID-19 mortality were obtained for 74 countries from the Allele Frequency Net Database and worldometer.info. Association between allele frequency of each HLA and mortality was assessed by linear regression followed by multivariable regression. Subsequently, association of HLA-C*05 to its receptor <i>KIR2DS4fl</i>, expressed on natural killer (NK) cells, and differential mortality to historic pandemics were analyzed. Results: HLA-A*01, -B*07, -B*08, -B*44 and -C*05 were significantly associated with the risk of deaths (adjusted <i>p</i> = 0.040, 0.00081, 0.047, 0.0022, 0.00032, respectively), but only HLA-C*05 remained statistically significant (<i>p</i> = 0.000027) after multivariable regression. A 1% increase in the allele frequency of HLA-C*05 was associated with an increase of 44 deaths/million. Countries with different mortality could be categorized by the distribution of HLA-C*05 and its receptor <i>KIR2DS4fl</i>, which in combination cause NK cell-induced hyperactive immune response. Countries with similar ethnic and/or geographic background responded in a similar pattern to each pandemic. Conclusions: we demonstrated that allele frequency of HLA-C*05 and the distribution pattern with its receptor <i>KIR2DS4fl</i> strongly correlated with COVID-19 mortality. Host genetic variance of innate immunity may contribute to the difference in mortality among various countries and further investigation using patient samples is warranted. |
| first_indexed | 2024-03-10T14:41:16Z |
| format | Article |
| id | doaj.art-bc425215c4564b0a82ebb8b37f918bc4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T14:41:16Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bc425215c4564b0a82ebb8b37f918bc42023-11-20T21:45:45ZengMDPI AGViruses1999-49152020-11-011211133310.3390/v12111333Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 MortalityAtsushi Sakuraba0Haider Haider1Toshiro Sato2Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, IL 60637, USASection of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, IL 60637, USADepartment of Organoid Medicine, Keio University School of Medicine, Tokyo 160-8582, JapanBackground: coronavirus disease 2019 (COVID-19) causes severe illness including cytokine storms, but mortality among countries differs largely. In the present study, we investigated the association between human leukocyte antigen (HLA) class I, which plays a major role in susceptibility to viral infections, and the mortality of COVID-19. Methods: data of allele frequencies of HLA-A, -B and -C and COVID-19 mortality were obtained for 74 countries from the Allele Frequency Net Database and worldometer.info. Association between allele frequency of each HLA and mortality was assessed by linear regression followed by multivariable regression. Subsequently, association of HLA-C*05 to its receptor <i>KIR2DS4fl</i>, expressed on natural killer (NK) cells, and differential mortality to historic pandemics were analyzed. Results: HLA-A*01, -B*07, -B*08, -B*44 and -C*05 were significantly associated with the risk of deaths (adjusted <i>p</i> = 0.040, 0.00081, 0.047, 0.0022, 0.00032, respectively), but only HLA-C*05 remained statistically significant (<i>p</i> = 0.000027) after multivariable regression. A 1% increase in the allele frequency of HLA-C*05 was associated with an increase of 44 deaths/million. Countries with different mortality could be categorized by the distribution of HLA-C*05 and its receptor <i>KIR2DS4fl</i>, which in combination cause NK cell-induced hyperactive immune response. Countries with similar ethnic and/or geographic background responded in a similar pattern to each pandemic. Conclusions: we demonstrated that allele frequency of HLA-C*05 and the distribution pattern with its receptor <i>KIR2DS4fl</i> strongly correlated with COVID-19 mortality. Host genetic variance of innate immunity may contribute to the difference in mortality among various countries and further investigation using patient samples is warranted.https://www.mdpi.com/1999-4915/12/11/1333COVID-19mortalityHLAgeneglobalinnate immunity |
| spellingShingle | Atsushi Sakuraba Haider Haider Toshiro Sato Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality Viruses COVID-19 mortality HLA gene global innate immunity |
| title | Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality |
| title_full | Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality |
| title_fullStr | Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality |
| title_full_unstemmed | Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality |
| title_short | Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality |
| title_sort | population difference in allele frequency of hla c 05 and its correlation with covid 19 mortality |
| topic | COVID-19 mortality HLA gene global innate immunity |
| url | https://www.mdpi.com/1999-4915/12/11/1333 |
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