Arg753Gln Polymorphisms in the Toll-Like Receptor 2 Gene are Associated with Cytomegalovirus Infection in Egyptian Bone Marrow Recipients

Abstract

Background: Previous studies have shown that cytomegalovirus (CMV) induced innate immune response via activation of Toll-like receptor 2 (TLR2). The association between CMV among specific single-nucleotide polymorphisms (SNPs) in the TLR2 gene was also investigated.

Objective: This study investigated the relationship between specific SNPs in the TLR2 gene (G>A), TLR2-Arg753Gln (rs5743708), and CMV replication after bone marrow transplantation.

Methods: The TLR2-Arg753Gln SNP was genotyped in 181 patients after bone marrow transplantation: 83 and 98 patients with and without CMV infection, respectively. CMV load was determined in serially collected blood samples using real-time PCR. Genotyping was performed using specific sequence primer PCR (SSP-PCR), and the results were confirmed by restriction fragment length polymorphism (RFLP) analysis of the PCR-amplified fragments for GG (wild type), GA and AA identification.

Results: Roughly, 85% of the patients screened for the presence of the TLR2-Arg753Gln were GG homozygous, and 15% were GA heterozygous; no patients were homozygous for the mutant allele (A). The GA heterozygous allele was more frequent in the CMV-infected group after bone marrow transplantation.

Conclusion: To our knowledge, this is a novel observation that supports the notion that the functional missense mutation (TLR2-Arg753Gln polymorphism) is possibly associated with CMV replication after bone marrow transplantation. This suggests a role for TLR2 in the innate immune response of human CMV infection in Egyptian bone marrow recipients.

Keywords: Arg753Gln; Toll-like receptor 2; bone marrow transplantation; cytomegalovirus; rs5743708; single-nucleotide polymorphisms (SNPs)..