title: Interferon-gamma gene polymorphism +874 A/T is associated with an increased risk of cytomegalovirus infection among Hispanic renal transplant recipients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mendez National Institute of Transplantation, Los Angeles, California, USA; Western University of Health Sciences, Pomona, California, USA; Transplant Research Institute, Los Angeles, California, USA; St. Vincent Medical Center, Los Angeles, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Vu
authors.forename: T
authors.initials: T
authors.lastname: Shah
authors.forename: J
authors.initials: J
authors.lastname: Ansari
authors.forename: P
authors.initials: P
authors.lastname: Sakharkar
authors.forename: Q
authors.initials: Q
authors.lastname: Yasir
authors.forename: R
authors.initials: R
authors.lastname: Naraghi
authors.forename: I
authors.initials: I
authors.lastname: Hutchinson
authors.forename: D
authors.initials: D
authors.lastname: Min
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000235:genetics* / Q000821:virology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Hispanic patients; cytomegalovirus; gene polymorphism; interferon gamma; kidney allograft