Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients. Viruses 2023 Nov 08;15(11)
Date
11/25/2023Pubmed ID
38005904Pubmed Central ID
PMC10674338DOI
10.3390/v15112227Scopus ID
2-s2.0-85177737555 (requires institutional sign-in at Scopus site)Abstract
Human cytomegalovirus (CMV) is a major pathogen after solid organ transplantation, leading to high morbidity and mortality. Transplantation from a CMV-seropositive donor to a CMV-seronegative recipient (D+/R-) is associated with high risk of CMV disease. However, that risk is not uniform, suggesting a role for host factors in immune control of CMV. To identify host genetic factors that control CMV DNAemia post transplantation, we performed a whole-exome association study in two cohorts of D+/R- kidney transplant recipients. Quantitative CMV DNA was measured for at least one year following transplantation. Several CMV-protective single-nucleotide polymorphisms (SNPs) were identified in the first cohort (72 patients) but were not reproducible in the second cohort (126 patients). A meta-analysis of both cohorts revealed several SNPs that were significantly associated with protection from CMV DNAemia. The copy number variation of several genes was significantly different between recipients with and without CMV DNAemia. Amongst patients with CMV DNAemia in the second cohort, several variants of interest (p < 5 × 10-5), the most common of which was NLRC5, were associated with peak viral load. We provide new predictive genetic markers for protection of CMV DNAemia. These markers should be validated in larger cohorts.
Author List
Shapira G, Volkov H, Fabian I, Mohr DW, Bettinotti M, Shomron N, Avery RK, Arav-Boger RAuthor
Ravit Boger MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antiviral AgentsCytomegalovirus
Cytomegalovirus Infections
DNA Copy Number Variations
DNA, Viral
Genomics
Humans
Intracellular Signaling Peptides and Proteins
Kidney Transplantation
Retrospective Studies
Transplant Recipients
