Skip to main content
SpringerLink
Log in

Genetic Polymorphisms in the Host and COVID-19 Infection

  • Chapter
  • First Online:
Coronavirus Disease - COVID-19

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1318))

Abstract

The outbreak of the COVID-19 pandemic shows a marked geographical variation in its prevalence and mortality. The question arises if the host genetic variation may (partly) affect the prevalence and mortality of COVID-19. We postulated that the geographical variation of human polymorphisms might partly explain the variable prevalence of the infection. We investigated some candidate genes that have the potential to play a role in the immune defense against COVID-19: complement component 3 (C3), galactoside 2-alpha-L-fucosyltransferase 2 (FUT2), haptoglobin (Hp), vitamin D binding protein (DBP), human homeostatic iron regulator protein (HFE), cystic fibrosis transmembrane conductance regulator (CFTR), and angiotensin-converting enzyme 1 (ACE1). In a univariate approach, ACE1 D/I, C3, CFTR, and HFE polymorphisms correlated significantly with COVID-19 prevalence/mortality, whereas Hp and FUT2 polymorphism did not show any significant correlations. In a multivariate analysis, only ACE1 D/I and C3 polymorphisms were determinants for COVID-19 prevalence/mortality. The other polymorphisms (CFTR, DBP, FUT2, HFE, and Hp) did not correlate with COVID-19 prevalence/mortality. Whereas ACE1 D/I polymorphism shows functional links with ACE2 (which is the receptor for the virus) in COVID-19, C3 can act as a critical step in the virus-induced inflammation. Our findings plead against a bystander role of the polymorphisms as a marker for historical migrations, which comigrate with causal genes involved in COVID-19 infection. Further studies are required to assess the clinical outcome of COVID-19 in C3S and ACE1 D allele carriers and to study the role of C3 and ACE1 D/I polymorphisms in COVID-19 and their potential effects on treatment response.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alfonso-Sánchez MA, Pérez-Miranda AM, García-Obregón S, Peña JA (2010) An evolutionary approach to the high frequency of the Delta F508 CFTR mutation in European populations. Med Hypotheses 74:989–992

    Article  PubMed  CAS  Google Scholar 

  • Alper CA, Propp RP (1968) Genetic polymorphism of the third component of human complement (C'3). J Clin Invest 47:2181–2191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barton JC, Edwards CQ, Acton RT (2015) HFE gene: structure, function, mutations, and associated iron abnormalities. Gene 574:179–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borzan V, TomaÅ¡ević B, Kurbel S (2014) Hypothesis: possible respiratory advantages for heterozygote carriers of cystic fibrosis linked mutations during dusty climate of last glaciation. J Theor Biol 363:164–168

    Article  PubMed  Google Scholar 

  • Bradbury J (2004) Ancient footsteps in our genes: evolution and human disease. Gene variants selected during evolution may underlie many common diseases. Lancet 363:952–953

    Article  PubMed  Google Scholar 

  • Bucher J, Boelle PY, Hubert D, Lebourgeois M, Stremler N, Durieu I, Bremont F, Deneuville E, Delaisi B, Corvol H, Bassinet L, Grenet D, Remus N, Vodoff MV, Boussaud V, Troussier F, Leruez-Ville M, Treluyer JM, Launay O, Sermet-Gaudelus I (2016) Lessons from a French collaborative case-control study in cystic fibrosis patients during the 2009 a/H1N1 influenza pandemy. BMC Infect Dis 16:55

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Carroll MC (1998) The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 16:545–568

    Article  CAS  PubMed  Google Scholar 

  • Cavalli-Sforza LL, Menozzi P, Piazza A (1994) The history and geography of human genes. Princeton University Press, Princeton, pp 1–1088

    Google Scholar 

  • Colombo C, Battezzati PM, Lucidi V, Magazzù G, Motta V, Alicandro G, Taccetti G, Repetto T (2011) Influenza a/H1N1 in patients with cystic fibrosis in Italy: a multicentre cohort study. Thorax 66:260–261

    Article  PubMed  Google Scholar 

  • Colombo C, Burgel PR, Gartner S, van Koningsbruggen-Rietschel S, Naehrlich L, Sermet-Gaudelus I, Southern KW (2020) Impact of COVID-19 on people with cystic fibrosis. Lancet Respir Med 8:e35–e36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Damman J, Daha MR, Leuvenink HG, van Goor H, Hillebrands JL, Dijk MC, Hepkema BG, Snieder H, Born J, de Borst MH, Bakker SJ, Navis GJ, Ploeg RJ, Seelen MA (2012) Association of complement C3 gene variants with renal transplant outcome of deceased cardiac dead donor kidneys. Am J Transplant 12:660–668

    Article  CAS  PubMed  Google Scholar 

  • Delanghe JR, Langlois MR, Boelaert JR, Van Acker J, Van Wanzeele F, van der Groen G, Hemmer R, Verhofstede C, De Buyzere M, De Bacquer D, Arendt V, Plum J (1998) Haptoglobin polymorphism, iron metabolism and mortality in HIV infection. AIDS 12:1027–1032

    Article  CAS  PubMed  Google Scholar 

  • Delanghe J, Speeckaert M, De Buyzere ML, Langlois M, Torck M (2012) Human plasma protein polymorphisms and the persistence of cultural diversity. Proc Natl Acad Sci U S A 109:E2914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delanghe JR, Speeckaert R, Speeckaert MM (2014) Complement C3 and its polymorphism: biological and clinical consequences. Pathology 46:1–10

    Article  CAS  PubMed  Google Scholar 

  • Delanghe JR, Speeckaert R, Speeckaert MM (2015) Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best Pract Res Clin Endocrinol Metab 29:773–786

    Article  CAS  PubMed  Google Scholar 

  • Delanghe JR, Speeckaert MM, De Buyzere ML (2020a) COVID-19 infections are also affected by human ACE1 D/I polymorphism. Clin Chem Lab Med 58:1125–1126

    Google Scholar 

  • Delanghe JR, Speeckaert MM, De Buyzere ML (2020b) The host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections. Clin Chim Acta 505:192–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dhillon N, Walsh L, Krüger B, Mehrotra A, Ward SC, Godbold J, Radwan M, Schiano T, Murphy B, Schröppel B (2010) Complement component C3 allotypes and outcomes in liver transplantation. Liver Transpl 16:198–203

    Article  PubMed  Google Scholar 

  • Diurno F, Numis FG, Porta G, Cirillo F, Maddaluno S, Ragozzino A, De Negri P, Di Gennaro C, Pagano A, Allegorico E, Bressy L, Bosso G, Ferrara A, Serra C, Montisci A, D'Amico M, Schiano Lo Morello S, Di Costanzo G, Tucci AG, Marchetti P, Di Vincenzo U, Sorrentino I, Casciotta A, Fusco M, Buonerba C, Berretta M, Ceccarelli M, Nunnari G, Diessa Y, Cicala S, Facchini G (2020) Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci 24:4040–4047

    Google Scholar 

  • Farrell PM (2008) The prevalence of cystic fibrosis in the European Union. J Cyst Fibros 7:450–453

    Article  PubMed  Google Scholar 

  • Ge L, Trujillo G, Miller EJ, Kew RR (2014) Circulating complexes of the vitamin D binding protein with G-actin induce lung inflammation by targeting endothelial cells. Immunobiology 219:198–207

    Article  CAS  PubMed  Google Scholar 

  • Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS (2018) Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. MBio 9

    Google Scholar 

  • Henry S, Oriol R, Samuelsson B (1995) Lewis histo-blood group system and associated secretory phenotypes. Vox Sang 69:166–182

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Zhao G, Song N, Li P, Chen Y, Guo Y, Li J, Du L, Jiang S, Guo R, Sun S, Zhou Y (2018) Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerg Microbes Infect 7(77)

    Google Scholar 

  • Kasvosve I, Speeckaert MM, Speeckaert R, Masukume G, Delanghe JR (2010) Haptoglobin polymorphism and infection. Adv Clin Chem 50:23–46

    Article  CAS  PubMed  Google Scholar 

  • Kuba K, Imai Y, Penninger JM (2006) Angiotensin-converting enzyme 2 in lung diseases. Curr Opin Pharmacol 6:271–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42:1589–1600

    Article  CAS  PubMed  Google Scholar 

  • Lee WM, Galbraith RM (1992) The extracellular actin-scavenger system and actin toxicity. N Engl J Med 326:1335–1341

    Article  CAS  PubMed  Google Scholar 

  • Lind SE, Smith DB, Janmey PA, Stossel TP (1986) Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation. J Clin Invest 78:736–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu PP, Blet A, Smyth D, Li H (2020) The science underlying COVID-19: implications for the cardiovascular system. Circulation 142(1):68–78

    Article  CAS  PubMed  Google Scholar 

  • Lucotte G, Dieterlen F (2003) A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation? Blood Cells Mol Dis 31:262–267

    Article  CAS  PubMed  Google Scholar 

  • Mastellos DC, Ricklin D, Lambris JD (2019) Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov 18:707–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meier U, Gressner O, Lammert F, Gressner AM (2006) Gc-globulin: roles in response to injury. Clin Chem 52:1247–1253

    Article  CAS  PubMed  Google Scholar 

  • Pallet N, Thervet E (2012) The genetics of kidney transplantation. Hum Genet 131:317–323

    Article  PubMed  Google Scholar 

  • Poznansky MC, Clissold PM, Lachmann PJ (1989) The difference between human C3F and C3S results from a single amino acid change from an asparagine to an aspartate residue at position 1216 on the alpha chain of the complement component, C3. J Immunol 143:3860–3862

    Article  CAS  PubMed  Google Scholar 

  • Reuben A, Chung JW, Lapointe R, Santos MM (2017) The hemochromatosis protein HFE 20 years later: an emerging role in antigen presentation and in the immune system. Immun Inflammation Dis 5:218–232

    Article  CAS  Google Scholar 

  • Risitano AM, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD (2020) Complement as a target in COVID-19? Nat Rev Immunol 20:343–344

    Article  CAS  PubMed  Google Scholar 

  • Rydell GE, Kindberg E, Larson G, Svensson L (2011) Susceptibility to winter vomiting disease: a sweet matter. Rev Med Virol 21:370–382

    Article  PubMed  Google Scholar 

  • Saab YB, Gard PR, Overall AD (2007) The geographic distribution of the ACE II genotype: a novel finding. Genet Res 89:259–267

    Article  CAS  PubMed  Google Scholar 

  • Schmidt SM (2020) The role of iron in viral infections. Front Biosci (Landmark Ed) 25:893–911

    Article  CAS  Google Scholar 

  • Sokal (1991) The continental population structure of Europe. Ann Rev Anthropol 20:119–140

    Article  Google Scholar 

  • Sokal RR, Oden NL, Wilson C (1991) Genetic evidence for the spread of agriculture in Europe by demic diffusion. Nature 351:143–145

    Article  CAS  PubMed  Google Scholar 

  • Speeckaert M, Huang G, Delanghe JR, Taes YE (2006) Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta 372:33–42

    Article  CAS  PubMed  Google Scholar 

  • Teisberg P (1970) High voltage agarose gel electrophoresis in the study of C 3 polymorphism. Vox Sang 19:47–56

    Article  CAS  PubMed  Google Scholar 

  • Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 395:1417–1418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • www.worldometers.info/coronavirus/countries

  • Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q (2020) Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367:1444–1448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 14:185–192

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Diagnostic Sciences, Ghent University, Ghent, Belgium

    Joris R. Delanghe

  2. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Ghent, Belgium

    Joris R. Delanghe

  3. Department of Internal Medicine, Ghent University, Ghent, Belgium

    Marc L. De Buyzere & Marijn M. Speeckaert

  4. Research Foundation-Flanders (FWO), Ghent, Belgium

    Marijn M. Speeckaert

Authors
  1. Joris R. Delanghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc L. De Buyzere
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marijn M. Speeckaert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joris R. Delanghe .

Editor information

Editors and Affiliations

  1. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Delanghe, J.R., De Buyzere, M.L., Speeckaert, M.M. (2021). Genetic Polymorphisms in the Host and COVID-19 Infection. In: Rezaei, N. (eds) Coronavirus Disease - COVID-19. Advances in Experimental Medicine and Biology, vol 1318. Springer, Cham. https://doi.org/10.1007/978-3-030-63761-3_7

Download citation

Publish with us

Policies and ethics

Search

Navigation