Interferon-gamma gene polymorphism +874 A/T is associated with an increased risk of cytomegalovirus infection among Hispanic renal transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is the most common cause of viral infection, causing morbidity and mortality among renal transplant recipients (RTRs). Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and interferon-gamma (IFN-γ) have been shown to possess antiviral properties, and their polymorphisms are associated with disease outcome. The aim was to investigate the association of gene polymorphisms in IL-10, IFN-γ, and TNF-α with CMV infection in RTRs. METHODS: IL-10 -1082 A>G, -592 A>C; TNF-α -308 A>G; and IFN-γ +874 A>T gene polymorphisms were studied in 247 Hispanic RTRs (52 RTRs with CMV infection and 195 without CMV infection), using DNA-based polymerase chain reaction with sequence-specific primers and restriction. RESULTS: Median time to CMV infection was 8 months, with a mean peak CMV viral load of 25,314 copies/mL. Patients with donor-positive/recipient-negative (D+/R-) serostatus were found to be associated with a high risk of CMV infection (P = 0.001). A statistically significant correlation was found between IFN-γ +874 A>T polymorphism and the risk of CMV infection. The IFN-γ +874 AA genotype was associated with a 3.4-fold increased risk for the CMV-infected group compared to the non-CMV group (odds ratio = 3.4, 95% confidence interval = 1.24-9.34, P = 0.01). The association was independently significant in multiple logistic regression (P = 0.01), along with serologic status D+/R-, acute rejection, and anti-thymocyte globulin induction. The allelic as well as genotypic frequencies of TNF-α and IL-10 did not significantly differ between the CMV-infection group and the control group. Individuals with IFN-γ +874 AT and AA genotypes exhibited higher risk of allograft loss. CONCLUSION: This study suggested that RTRs with variant homozygous IFN-γ AA genotype were at risk of CMV infection, whereas the high producer IFN-γ +874 TT genotype appears to be associated with lower risk of CMV infection.