The Role of Immunogenetics in COVID-19
Abstract
1. Introduction
2. AB0 Groups
3. HLA
3.1. Incidence and Susceptibility
3.2. Disease Severity
3.3. Mortality
3.4. Transplanted Patients
3.5. Functional and Mechanistic Considerations
4. Other Immune Response Genes
4.1. Type I Interferons and Players of Their Molecular Pathways
4.2. Other Cytokines, Chemokines and Their Signaling Pathways
4.3. Other Genetic Determinants of Establishment/Maintenance/Resolution of the Immune Response and Antigen Presentation
5. Discussion
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACE2 | Angiotensin-converting enzyme 2 |
AD | Autosomal-dominant |
AH | Ancestral haplotype |
AIDS | Acquired immunodeficiency syndrome |
APACHE | Acute Physiology and Chronic Health Evaluation |
ApoE | Apoliprotein E |
AR | Autosomal-recessive |
ARDS | Acute respiratory distress syndrome |
CD40L | CD40 ligand |
CDC | Centers for Disease Control and Prevention |
CCR2 | C-C Motif Chemokine Receptor 2 |
CCR3 | C-C Motif Chemokine Receptor 3 |
CCR5 | C-C Motif Chemokine Receptor 5 |
CCR9 | C-C Motif Chemokine Receptor 9 |
COVID-19 | Coronavirus disease 19 |
CRP | C-reactive protein |
CXCR3 | C-X-C Motif Chemokine Receptor 3 |
CXCR6 | C-X-C Motif Chemokine Receptor 6 |
DPP | Dipeptidyl peptidase |
EBV | Epstein-Barr Virus |
ECMO | Extracorporeal membrane oxygenation |
eQTL | Expression quantitative locus |
FOXP3 | Forkhead box p3 |
GM | Immunoglobulin G heavy chain |
GOLGA3 | Golgin subfamily A 3 |
GOLGA8B | Golgin A8 family member B |
GWAS | Genome wide association study |
HIV | Human immunodeficiency virus |
HLA | Human Leukocyte Antigens |
ICU | Intensive care unit |
IFITM3 | Interferon-induced transmembrane protein 3 |
IFNB1 | Interferon β 1 |
IFN-α | Interferon-α |
IFN-β | Interferon-β |
IFN-γ | Interferon-γ |
IFNAR1 | IFN-α receptor 1 |
IFNAR2 | IFN-α receptor 2 |
IL-1β | Interleukin-1β |
IL-6 | Interleukin-6 |
IL-10 | Interleukin-10 |
IL-17A | Interleukin-17A |
IL-17F | Interleukin-17F |
IL-21 | Interleukin-21 |
IP-10 | Interferon γ-induced protein-10 |
IRF | IFN regulatory factors |
ISG15 | Ubiquitin-like modifier ISG15 |
KIR | Killer Immunoglobulin Receptors |
KIR2DL2 | Killer Cell Immunoglobulin-Like Receptor 2DL2 |
KIR2DL3 | Killer Cell Immunoglobulin-Like Receptor 2DL3 |
LAPTM4B | Lysosomal Protein Transmembrane 4 β |
MIP-1α | Macrophage inflammatory protein 1α |
MIP-1β | Macrophage inflammatory protein 1β |
MMR | Measles, mumps, and rubella |
MST1R | Macrophage stimulating 1 receptor |
NEMO/IKBKG | NF-κB essential modulator |
NK | Natural Killer |
OAS | 2’-5’-Oligoadenylate synthetase |
PHA | Phytohemagglutinin |
PKR | IFN-induced, double-stranded RNA-activated protein kinase |
pLOF | Predicted to be loss-of-function |
PRKRA | Protein Activator of The Interferon-Induced Protein Kinase |
RBC | Red blood cells |
SNP | Single nucleotide polymorphism |
SOFA | Sepsis-related Organ Failure Assessment |
STAT1 | Signal transducer and activator of transcription 1 |
STAT2 | Signal transducer and activator of transcription 2 |
TBK1 | TANK binding kinase 1 |
TICAM1/TRIF | TIR-domain containing adaptor inducing IFN-β |
TLR | Toll like receptor |
TMEM189 | Transmembrane protein 189 |
TMPRSS2 | Transmembrane protease serine protease 2 |
TNF-α | Tumor necrosis factor-α |
TRAF3 | TNF Receptor Associated Factor 3 |
UBE2V1 | Ubiquitin-conjugating enzyme E2 variant 1 |
UNC93B1 | Unc-93 homolog B1 |
UTR | Untranslated region |
VEGF | Vascular endothelial growth factor |
VWF | von Willebrand factor |
WSB1 | WD Repeat And SOCS Box Containing 1 |
XCL1 | X-C Motif Chemokine Ligand 1 |
XCR1 | X-C Motif Chemokine Receptor 1 |
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Group/Locus | Variant | Outcome | p | OR (95% CI) | RR (95%CI) | Refs. |
---|---|---|---|---|---|---|
A | ||||||
Susceptibility | 0.027 | 1.21 (1.02–1.43) | [21] | |||
Susceptibility | * 0.04 | * 1.33 (1.02–1.73) | [24] | |||
Susceptibility | 0.0024 | 1.23 (1.08–1.41) | [25] | |||
Susceptibility | <0.001 | 1.09 (1.02–1.13) | [27] | |||
Susceptibility (1) | <0.001 | 1.249 (1.114–1.440) | [26] | |||
Susceptibility (2) | 0.03 | 1.3 (1.02–1.66) | [29] | |||
Respiratory failure | * 1.48×10−4 | * 1.45 (1.20–1.75) | [28] | |||
Mortality | 0.008 | 1.482 (1.113–1.972) | [21] | |||
AB | ||||||
Susceptibility | * 0.035 | * 1.37 (1.02–1.83) | [30] | |||
B | ||||||
Susceptibility | * 0.004 | * 1.28 (1.08–1.52) | [30] | |||
0 | ||||||
Susceptibility | <0.001 | 0.67 (0.60–0.75) | [21] | |||
Susceptibility | 0.0006 | 0.787 (0.69–0.90) | [25] | |||
Susceptibility | <0.001 | 0.87 (0.82–0.91) | [27] | |||
Susceptibility | * 0.007 | 0.84 (0.75–0.95) | [30] | |||
Susceptibility (1) | <0.001 | 0.699 (0.635–0.770) | [26] | |||
Respiratory failure | * 1.06×10−5 | * 0.65 (0.53–0.79) | [28] | |||
Mortality | 0.014 | 0.660 (0.479–0.911) | [21] | |||
Locus AB0 | ||||||
rs657152 (A) | Respiratory failure | * 5.35×10−7 | * 1.39 (1.22–1.59) | [28] |
Variable | Allele/Serotype | p | OR (95%CI) | Regression Coefficient | Growth Rate (95%CI) | Refs. |
---|---|---|---|---|---|---|
Incidence | B*44 | 0.05 | 0.1484 | 1.16 (1–1.35%) | [39] | |
C*01 | 0.042 | 0.1747 | 1.19 (1.01–1.41%) | [39] | ||
Susceptibility | B*15:27 | 0.030 | 3.59 (1.72–7.50) § | [45] | ||
B46 | n.s. | [46] | ||||
B22 | 0.032 | 1.71 (1.23–2.38) § | [46] | |||
C*07:29 | 0.025 | 130.20 (5.28–3211) § | [45] | |||
DQB1*06 | 0.0468 # | 1.96 (1.19–3.22) #§ | [47] | |||
DRB1*08 | 0.010 # | 1.814 (1.151–2.860) # | [29] | |||
Severity | A | n.s. | [28] | |||
A*11:01 | 0.008 | 2.33 | [10] | |||
B22 | n.s. | [46] | ||||
B27 | n.s. | [46,48] | ||||
B*27:07 | * 0.004 | [41] | ||||
B46 | n.s. | [46] | ||||
B*51:01 | 0.007 | 3.38 | [10] | |||
C | n.s. | [28] | ||||
C*14:02 | 0.003 | 4.75 | [10] | |||
DPB1*03:01 | 0.037 | 0.09 | [10] | |||
DQA1*01:01 | 0.039 | 6.05 | [10] | |||
DQB1 | n.s. | [28] | ||||
DQB1*06:02 | 0.016 | [41] | ||||
DRB1 | n.s. | [28] | ||||
DRB1*01:01 | 0.02 | 13.7 | [10] | |||
DRB1*12:01 | 0.045 | 0.18 | [10] | |||
DRB1*14:04 | 0.01 | 15.1 | [10] | |||
DRB1*15:01 | 0.048 | [37] | ||||
A*11 | 0.04 (1) | 7.693 (1.063–55.65) (1) | [40] | |||
0.02 (2) | 11.858 (1.524–92.273) (2) | [40] | ||||
Mortality | C*01 | 0.04 (1) | 11.182 (1.053–118.7) (1) | [40] | ||
0.02 (2) | 17.604 (1.629–190.211) (2) | [40] | ||||
DQB1*04 | 0.03 (1) | 9.963 (1.235–80.358) (1) | [40] | |||
DRB1*08 | 0.01 # | 8.6 (1.7–43.9) # | [29] |
Gene/Locus | Variant/ Position | Reference/ Other Allele | Altered/ Risk Allele | Protein Variant | Type | p | OR (95%CI) | Outcome | Refs. |
---|---|---|---|---|---|---|---|---|---|
TLR3 | § 187003852 | AT | A | p.Ser339fs | pLOF | 0.01 | 8.28 (1.04–65.64) | severity | [113] |
TLR3 | § 187005146 | G | A | p.Trp769 * | pLOF | ||||
UNC93B1 | § 67770598 | C | A | p.Glu96 * | pLOF | ||||
TBK1 | § 64875731 | C | T | p.Arg308 * | pLOF | ||||
IRF7 | § 615095 | A | C | p.Arg7fs | pLOF | ||||
IRF7 | § 614300 | G | A | p.Gln185 * | pLOF | ||||
IRF7 | § 613966 | CGGGCTGGGGCCCG | C | p.Pro246fs | pLOF | ||||
IRF7 | § 613353 | G | GC | p.Pro364fs | pLOF | ||||
IFNAR2 | § 34621038 | AGATTGTTGGTTTT | A | p.Glu140fs | pLOF | ||||
IFNAR2 | rs2236757 | G | A | 4.99 × 10−8 | 1.28 | severity | [117] | ||
OAS3 | rs10735079 | G | A | 1.65 × 10−8 | 1.29 | severity | [117] | ||
IFITM3 | rs12252 | T | C | # 0.0093 | # 6.37 | severity | [118] | ||
0.025 | 1.93 (1.09–3.46) | severity | [119] | ||||||
PRKRA | I226N | 0.02 | severity | [120] | |||||
TNF-α | rs1800629 | G | A | ° <0.001 | age > 60 | [121] | |||
° <0.001 | lymphopenia | [121] | |||||||
° 0.009 | high CRP | [121] | |||||||
° <0.001 | high ferritin | [121] | |||||||
° <0.001 | severity | [121] | |||||||
† 0.045 | severity | [121] | |||||||
3p21.31 | rs11385942 | G | GA | 1.15 × 10−10 | 1.77 (1.48–2.11) | respiratory failure | [28] | ||
0.003 | 1.56 (1.17–2.01) | mechanical ventilation | [28] | ||||||
TMEM189UBE2V1 | rs6020298 | G | A | 4.1 × 10–6 | 1.2 | severity | [10] | ||
DPP9 | rs2109069 | G | A | 3.98 × 10−12 | 1.36 | severity | [117] | ||
GOLGA8B | rs200975425 | C | T | 9.4 × 10–10 | 5.4 | susceptibility | [10] | ||
LAPTM4B | P219L | 0.029 | [120] | ||||||
P220L | |||||||||
I109F | |||||||||
P50T | |||||||||
ApoE | e3 | e4 | 1.19 × 10–6 | 2.31 (1.65–3.24) | severity | [122] | |||
^ 0.009 | ^ 1.20 (1.05–1.37) | severity | [123] | ||||||
3.24 × 10−9 | 2.24 (1.72–2.93) | severity | [123] | ||||||
1.22 × 10–6 | 4.29 (2.38–7.72) | mortality | [123] |
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Pojero, F.; Candore, G.; Caruso, C.; Di Bona, D.; Groneberg, D.A.; Ligotti, M.E.; Accardi, G.; Aiello, A. The Role of Immunogenetics in COVID-19. Int. J. Mol. Sci. 2021, 22, 2636. https://doi.org/10.3390/ijms22052636
Pojero F, Candore G, Caruso C, Di Bona D, Groneberg DA, Ligotti ME, Accardi G, Aiello A. The Role of Immunogenetics in COVID-19. International Journal of Molecular Sciences. 2021; 22(5):2636. https://doi.org/10.3390/ijms22052636
Chicago/Turabian StylePojero, Fanny, Giuseppina Candore, Calogero Caruso, Danilo Di Bona, David A. Groneberg, Mattia E. Ligotti, Giulia Accardi, and Anna Aiello. 2021. "The Role of Immunogenetics in COVID-19" International Journal of Molecular Sciences 22, no. 5: 2636. https://doi.org/10.3390/ijms22052636
APA StylePojero, F., Candore, G., Caruso, C., Di Bona, D., Groneberg, D. A., Ligotti, M. E., Accardi, G., & Aiello, A. (2021). The Role of Immunogenetics in COVID-19. International Journal of Molecular Sciences, 22(5), 2636. https://doi.org/10.3390/ijms22052636