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Meta-Analysis
. 2023 Nov 8;15(11):2227.
doi: 10.3390/v15112227.

Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients

Guy Shapira  1   2 , Hadas Volkov  1   2 , Itai Fabian  1 , David W Mohr  3 , Maria Bettinotti  4 , Noam Shomron  1   2 , Robin K Avery  5 , Ravit Arav-Boger  6
Affiliations
Meta-Analysis

Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients

Guy Shapira et al. Viruses. .

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.

Keywords: CMV DNAemia; genetic susceptibility; human cytomegalovirus; kidney transplantation; whole-exome sequencing.

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Conflict of interest statement

The authors report no conflicts of interest. Robin Avery has been an investigator on studies funded by Aicuris (Wuppertal, Germany), Astellas (Tokyo, Japan), Astra-Zeneca (Tokyo, Japan), Chimerix (Durham, NC, USA), Merck (Darmstadt, Germany), Oxford Immunotec (Oxfordshire, UK), Qiagen (Hong Kong, China), Regeneron (New York, NY, USA), and Takeda (Tokyo, Japan). No personal financial remuneration was received; study/grant support only.

Figures

Figure 1
Figure 1
Manhattan plot of variants associated with CMV DNAemia in both cohorts of kidney transplant recipients. Each dot represents a variant, placed according to its genomic position (x-axis, labeled chromosome name) and the significance of the association (y-axis; -log10 (p-value); higher indicates higher significance). Associations that passed the significance threshold (p < 5 × 10−5) are labeled and colored (see Supplementary Methods S1 and S2).
Figure 2
Figure 2
Association analysis between CMV DNAemia and genetic variants in the dynein heavy chain domain 1 (DNHD1) locus, presented for cohort A, Caucasians only in cohort A, and cohort B. Each shape represents a single genetic variant, placed on the X−axis according to its genomic position in relation to genes (visualized on the bottom panel) and on the Y−axis (left side) according to the log−scaled p−value of association (each of the three top panels applies to a single cohort). The recombination rate is denoted by the thin blue line and the values on the Y-axis (right side). Leading SNP results are marked by larger symbols, surrounding SNPs are colored according to linkage.
See this image and copyright information in PMC

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