Cytokine gene polymorphisms affect reactivation of cytomegalovirus in patients with cancer

Abstract

Reactivation of cytomegalovirus (CMV) in the bloodstream may occur upon severe immune defect or suppression during lifetime. We performed a case controlled study to probe the effects of the host cytokine gene single nucleotide polymorphisms (SNPs) on CMV reactivation. The study subjects were patients with cancer but without stem cell transplantation. The cases were patients tested positive for CMV pp65 antigenemia and the controls were those tested negative. Each case was matched to two controls for similar underlying disease, sex, age, and CMV antibody test status. Ninety cases and 182 controls were chosen and typed for 48 SNPs within 13 cytokines. Alleles of three cytokines were found to be significantly associated with CMV reactivation. Associated with risk of CMV reactivation were the TGFβ1-2 allele (10C and 25G) with a hazard ratio (HR) of 1.97% and 95% confidence interval (CI) of 1.14–3.41 and the IL-4-3 allele (−1098T, −590T, and −33T) (HR, 2.08) (95% CI, 1.19–3.63); associated with protection was the IL-2-2 allele (−330T and +166G) (HR, 0.58) (95% CI, 0.35–0.97). Gene dosage, synergism, and antagonism among these alleles were also observed. Our results suggest roles of immunogenetic variations on the immunity against CMV, which may allow clinical CMV risk stratification. Further studies of these alleles are warranted.