Display options
Cite
Casto AM, Seo S, Levine DM, et al. Genetic variants associated with cytomegalovirus infection after allogeneic hematopoietic cell transplantation. Blood. 2021;138(17):1628-1636doi: 10.1182/blood.2021012153.
Casto, A. M., Seo, S., Levine, D. M., Storer, B. E., Dong, X., Hansen, J. A., Boeckh, M., & Martin, P. J. (2021). Genetic variants associated with cytomegalovirus infection after allogeneic hematopoietic cell transplantation. Blood, 138(17), 1628-1636. https://doi.org/10.1182/blood.2021012153
Casto, Amanda M, et al. "Genetic variants associated with cytomegalovirus infection after allogeneic hematopoietic cell transplantation." Blood vol. 138,17 (2021): 1628-1636. doi: https://doi.org/10.1182/blood.2021012153
Casto AM, Seo S, Levine DM, Storer BE, Dong X, Hansen JA, Boeckh M, Martin PJ. Genetic variants associated with cytomegalovirus infection after allogeneic hematopoietic cell transplantation. Blood. 2021 Oct 28;138(17):1628-1636. doi: 10.1182/blood.2021012153. PMID: 34269803; PMCID: PMC8554648.
Copy Download .nbib Format: NLM
Share it on

Blood. 2021 Oct 28;138(17):1628-1636. doi: 10.1182/blood.2021012153.

Genetic variants associated with cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Blood

Amanda M Casto, Sachiko Seo, David M Levine, Barry E Storer, Xinyuan Dong, John A Hansen, Michael Boeckh, Paul J Martin

Affiliations

  1. Department of Medicine, University of Washington School of Medicine, Seattle, WA.
  2. Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
  3. Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
  4. Department of Biostatistics, University of Washington, Seattle, WA; and.
  5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

PMID: 34269803 PMCID: PMC8554648 DOI: 10.1182/blood.2021012153

Abstract

Human cytomegalovirus (CMV) reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Despite routine screening for CMV reactivation and early antiviral treatment, the rates of CMV-related complications after HCT remain high. Genetic variants in both the donor and recipient have been associated with the risk of CMV reactivation and disease after HCT, but these associations have not been validated, and their clinical importance remains unclear. In this study, we assessed 117 candidate variants previously associated with CMV-related phenotypes for association with CMV reactivation and disease in a cohort of 2169 CMV-seropositive HCT recipients. We also carried out a genome-wide association study (GWAS) for CMV reactivation and disease in the same cohort. Both analyses used a prespecified discovery and replication approach to control the risk of false-positive results. Among the 117 candidate variants, our analysis implicates only the donor ABCB1 rs1045642 genotype as a risk factor for CMV reactivation. This synonymous variant in P-glycoprotein may influence the risk of CMV reactivation by altering the efflux of cyclosporine and tacrolimus from donor lymphocytes. In the GWAS analysis, the donor CDC42EP3 rs11686168 genotype approached the significance threshold for association with CMV reactivation, although we could not identify a mechanism to explain this association. The results of this study suggest that most genomic variants previously associated with CMV phenotypes do not significantly alter the risk for CMV reactivation or disease after HCT.

© 2021 by The American Society of Hematology.

References

  1. PLoS One. 2018 Jul 23;13(7):e0200221 - PubMed
  2. Blood. 2016 May 19;127(20):2427-38 - PubMed
  3. Pharmacogenet Genomics. 2008 Apr;18(4):307-15 - PubMed
  4. Blood. 2008 Feb 15;111(4):1816-9 - PubMed
  5. Clin Lymphoma. 2002 Sep;3(2):105-10 - PubMed
  6. Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238 - PubMed
  7. Clin Infect Dis. 2017 Jan 1;64(1):87-91 - PubMed
  8. Curr Opin Lipidol. 2014 Oct;25(5):333-8 - PubMed
  9. Biol Blood Marrow Transplant. 2009 Jun;15(6):694-703 - PubMed
  10. Lancet Haematol. 2016 Mar;3(3):e119-27 - PubMed
  11. Science. 2007 Jan 26;315(5811):525-8 - PubMed
  12. Biol Blood Marrow Transplant. 2000;6(3):280-8 - PubMed
  13. Cell Rep. 2016 Jun 28;16(1):186-200 - PubMed
  14. PLoS One. 2019 Sep 18;14(9):e0222336 - PubMed
  15. Biol Blood Marrow Transplant. 2012 Nov;18(11):1687-99 - PubMed
  16. Xenobiotica. 2019 Nov;49(11):1373-1378 - PubMed
  17. J Med Virol. 2015 Feb;87(2):248-55 - PubMed
  18. J Am Soc Nephrol. 2009 Jun;20(6):1404-15 - PubMed
  19. J Immunol. 2011 Aug 15;187(4):1529-35 - PubMed
  20. Biochem Soc Trans. 2016 Dec 15;44(6):1709-1716 - PubMed
  21. Transpl Infect Dis. 2021 Jun;23(3):e13548 - PubMed
  22. Bone Marrow Transplant. 2008 Aug;42 Suppl 1:S70-S72 - PubMed
  23. Drugs. 2018 Jul;78(11):1085-1103 - PubMed
  24. Am J Hum Genet. 2016 Jan 7;98(1):165-84 - PubMed
  25. Blood Adv. 2020 Jul 28;4(14):3224-3233 - PubMed
  26. Ther Drug Monit. 2013 Aug;35(4):459-65 - PubMed
  27. J Med Virol. 2014 May;86(5):838-44 - PubMed
  28. World J Transplant. 2015 Dec 24;5(4):287-91 - PubMed
  29. Drug Metab Lett. 2008 Apr;2(2):76-82 - PubMed
  30. Small GTPases. 2018 May 4;9(3):237-241 - PubMed
  31. Pharmacogenomics. 2010 May;11(5):703-14 - PubMed
  32. J Clin Microbiol. 2006 May;44(5):1847-50 - PubMed
  33. Transpl Infect Dis. 2012 Apr;14(2):141-8 - PubMed
  34. Haematologica. 2004 Oct;89(10):1248-52 - PubMed
  35. Transpl Infect Dis. 2010 Aug 1;12(4):322-9 - PubMed

Publication Types

Grant support