Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients
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...
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MDPI AG
2023-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/11/2227 |
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| author | Guy Shapira Hadas Volkov Itai Fabian David W. Mohr Maria Bettinotti Noam Shomron Robin K. Avery Ravit Arav-Boger |
| author_facet | Guy Shapira Hadas Volkov Itai Fabian David W. Mohr Maria Bettinotti Noam Shomron Robin K. Avery Ravit Arav-Boger |
| author_sort | Guy Shapira |
| collection | DOAJ |
| description | 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 (<i>p</i> < 5 × 10<sup>−5</sup>), 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. |
| first_indexed | 2024-03-09T16:22:37Z |
| format | Article |
| id | doaj.art-5b4c2c20f1ef416ab5d7833d0dd586b6 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T16:22:37Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-5b4c2c20f1ef416ab5d7833d0dd586b62023-11-24T15:10:53ZengMDPI AGViruses1999-49152023-11-011511222710.3390/v15112227Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant RecipientsGuy Shapira0Hadas Volkov1Itai Fabian2David W. Mohr3Maria Bettinotti4Noam Shomron5Robin K. Avery6Ravit Arav-Boger7Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelFaculty of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelFaculty of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelJohns Hopkins Genetic Resources Core Facility, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAImmunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAFaculty of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelDepartment of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, WI 53226, USAHuman 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 (<i>p</i> < 5 × 10<sup>−5</sup>), 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.https://www.mdpi.com/1999-4915/15/11/2227human cytomegaloviruskidney transplantationgenetic susceptibilitywhole-exome sequencingCMV DNAemia |
| spellingShingle | Guy Shapira Hadas Volkov Itai Fabian David W. Mohr Maria Bettinotti Noam Shomron Robin K. Avery Ravit Arav-Boger Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients Viruses human cytomegalovirus kidney transplantation genetic susceptibility whole-exome sequencing CMV DNAemia |
| title | Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients |
| title_full | Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients |
| title_fullStr | Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients |
| title_full_unstemmed | Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients |
| title_short | Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients |
| title_sort | genomic markers associated with cytomegalovirus dnaemia in kidney transplant recipients |
| topic | human cytomegalovirus kidney transplantation genetic susceptibility whole-exome sequencing CMV DNAemia |
| url | https://www.mdpi.com/1999-4915/15/11/2227 |
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