Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation.
BACKGROUND
Experimental data suggest that cytomegalovirus (CMV) initiates innate immunity through the activation of Toll-like receptor 2 (TLR2). To assess the clinical relevance of this experimental observation, we assessed the association between the specific single-nucleotide polymorphism that results in the substitution of arginine for glutamine in position 753 of TLR2 (the TLR2 Arg753Gln polymorphism) and CMV replication and disease after liver transplantation.


METHODS
Ninety-two liver transplant recipients with chronic hepatitis C were screened for the presence of the TLR2 Arg753Gln polymorphism. CMV load was determined in serially collected blood samples using CMV DNA polymerase chain reaction. Kaplan-Meier estimation and univariable and multivariable stepwise Cox proportional hazard models were used to assess associations.


RESULTS
The degree of CMV replication, as measured by CMV load, was significantly higher in patients who were homozygous (mean maximum viral load, 37,059 copies/mL) and heterozygous (mean maximum viral load, 29,718 copies/mL) for this polymorphism, compared with patients without the TLR2 Arg753Gln polymorphism (mean maximum viral load, 3252 copies/mL; P=.003). Kaplan-Meier survival analysis demonstrated an association between being homozygous for the TLR2 Arg753Gln polymorphism and CMV disease (P=.04). A multivariate Cox proportional hazard model demonstrated a trend towards a higher risk of CMV disease among patients who were homozygous for the TLR2 Arg753Gln polymorphism (hazard ratio, 1.91 [95% confidence interval, 0.91-3.40]; P=.08) after adjusting for patient age, CMV serostatus, and allograft rejection.


CONCLUSIONS
TLR2 Arg753Gln polymorphism is possibly associated with CMV replication and disease after liver transplantation. This novel clinical observation supports the potential role of TLR2 in the immunologic control of CMV infection in humans.
Kijpittayarit
Supha
S
Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Eid
Albert J
AJ
Brown
Robert A
RA
Paya
Carlos V
CV
Razonable
Raymund R
RR
D000328:Adult; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D005260:Female; D019698:Hepatitis C, Chronic / Q000601:surgery; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000379:methods; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2