4.7 Article

Homozygosity for the Toll-Like Receptor 2 R753Q Single-Nucleotide Polymorphism Is a Risk Factor for Cytomegalovirus Disease After Liver Transplantation

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JOURNAL OF INFECTIOUS DISEASES
卷 205, 期 4, 页码 639-646

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OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jir819

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  1. National Institutes of Health, National Center for Research Resources, Center for Translational Science Activities (NCRR CTSA) [UL1 RR024150]
  2. Clinical and Translational Science Activities, Mayo Clinic
  3. Mayo Transplant Center

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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.

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