Homozygosity for the toll-like receptor 2 R753Q single-nucleotide polymorphism is a risk factor for cytomegalovirus disease after liver transplantation.
Immunity against cytomegalovirus (CMV) is initiated after its recognition by Toll-like receptor 2 (TLR2). We assessed the association between a single-nucleotide polymorphism (SNP) that impairs TLR2 function and CMV disease in a cohort of 737 liver recipients. Ninety-two of 737 patients (7.1%, 10.9%, 12.3%, and 12.5% by 3, 6, 12, and 24 months, respectively) developed CMV disease. Kaplan-Meier estimation demonstrated an association between TLR2 R753Q SNP homozygosity and CMV disease (P = .044), especially tissue-invasive CMV disease (P = .001). A multivariate Cox proportional hazard model that accounted for other significant predictors demonstrated a significant association between TLR2 R753Q SNP homozygosity and tissue-invasive CMV disease (hazard ratio, 3.407; 95% confidence interval, 1.518-7.644; P = .0029). In conclusion, homozygosity for TLR2 R753Q SNP is a marker for CMV disease risk, especially for tissue-invasive disease, after liver transplantation. This observation supports the critical role of TLR2 in the pathogenesis of CMV disease in humans.
Division of Infectious Diseases, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Seung H
SH
Kang
Rima C
RC
Abdel-Massih
Robert A
RA
Brown
Ross A
RA
Dierkhising
Walter K
WK
Kremers
Raymund R
RR
Razonable
D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D055815:Young Adult
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2