PMID- 33233780
OWN - NLM
STAT- MEDLINE
DCOM- 20201209
LR  - 20240330
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 12
IP  - 11
DP  - 2020 Nov 20
TI  - Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with 
      COVID-19 Mortality.
LID - 10.3390/v12111333 [doi]
LID - 1333
AB  - 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 KIR2DS4fl, 
      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 p = 0.040, 0.00081, 
      0.047, 0.0022, 0.00032, respectively), but only HLA-C*05 remained statistically 
      significant (p = 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 KIR2DS4fl, 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 KIR2DS4fl 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.
FAU - Sakuraba, Atsushi
AU  - Sakuraba A
AD  - Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago 
      Medicine, Chicago, IL 60637, USA.
FAU - Haider, Haider
AU  - Haider H
AD  - Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago 
      Medicine, Chicago, IL 60637, USA.
FAU - Sato, Toshiro
AU  - Sato T
AD  - Department of Organoid Medicine, Keio University School of Medicine, Tokyo 
      160-8582, Japan.
AD  - Corona Virus Task Force, Keio University School of Medicine, Tokyo 160-8582, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20201120
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*05 antigen)
RN  - 0 (KIR2DS4 protein, human)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - COVID-19/*genetics/*mortality
MH  - Databases, Nucleic Acid
MH  - *Gene Frequency
MH  - *Genetic Association Studies
MH  - Global Health
MH  - HLA-C Antigens/*genetics
MH  - Host-Pathogen Interactions/genetics/immunology
MH  - Humans
MH  - Immunity, Innate
MH  - Multivariate Analysis
MH  - Pandemics
MH  - Receptors, KIR/genetics
MH  - Risk Factors
MH  - SARS-CoV-2
PMC - PMC7699862
OTO - NOTNLM
OT  - COVID-19
OT  - HLA
OT  - gene
OT  - global
OT  - innate immunity
OT  - mortality
OT  - selection
COIS- All authors have no conflicts of interest directly relevant to the content of 
      this article.
EDAT- 2020/11/26 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/11/01
CRDT- 2020/11/25 01:04
PHST- 2020/10/30 00:00 [received]
PHST- 2020/11/13 00:00 [revised]
PHST- 2020/11/19 00:00 [accepted]
PHST- 2020/11/25 01:04 [entrez]
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/11/01 00:00 [pmc-release]
AID - v12111333 [pii]
AID - viruses-12-01333 [pii]
AID - 10.3390/v12111333 [doi]
PST - epublish
SO  - Viruses. 2020 Nov 20;12(11):1333. doi: 10.3390/v12111333.