09.16.21

Genetic variants associated with post-allo HCT CMV infection

Casto A, Seo S, Levine D, et al. Genetic Variants Associated with Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation. Blood. 2021; (doi: 10.1182/blood.2021012153).

The majority of genomic variants previously associated with cytomegalovirus (CMV) phenotypes do not significantly affect the odds of CMV reactivation or disease after allogeneic hematopoietic cell transplantation (HCT), according to new research. The study evaluated 117 candidate variants previously associated with CMV-related phenotypes for a connection to CMV reactivation and disease in a group of 2,169 CMV-seropositive HCT recipients. A genome-wide association study (GWAS) assessed CMV reactivation and disease in the same cohort. To control the risk of false-positive results, both studies used a pre-specified discovery and replication method. Of the 117 candidate variants, only the donor ABCB1 rs1045642 genotype — a synonymous variant in P-glycoprotein — was identified as a risk factor for CMV reactivation after HCT, potentially by changing the efflux of cyclosporine and tacrolimus from donor lymphocytes. The GWAS analysis found that the donor CDC42EP3 rs11686168 genotype was close to the significance threshold for association with CMV reactivation following HCT; however, the mechanism to explain the association is not known.

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