Association of TLR4 polymorphisms and polyomavirus BK infection in liver transplant patients

Toll-like receptors (TLRs) may have a role in orchestrating the immune responses against polyomavirus BKV and also may influence liver transplant outcomes. However, the clinical relevance of this experimental observation has not been examined. Improving knowledge regarding details of genetic source of TLR polymorphisms can promote new therapeutic strategies to inhibit virus related clinical disorders in post-liver transplantation. Therefore, the Asp299Gly and Thr399Ile TLR4 polymorphisms were evaluated in liver transplanted patients with and without polyomavirus BK infection. In a cross sectional study, 144 liver transplant patients received allograft at Transplant Center of Namazi Hospital affiliated to Shiraz University of Medical Sciences who were recruited between years: 2014- 2015. Patients were followed for the graft outcome and acute rejection episode(s) and divided into two groups based on experiencing acute rejection or not. The genomic DNA of polyomavirus BK was diagnosed in studied patient using qualitative nested- PCR technique. Analysis of TLR4 gene polymorphisms were analyzed using PCR-RFLP protocols. The polyomavirus BK infection was found in 15 of 144 (10.4%) liver transplanted patients. A total of 14 of 15 (93.3%) and all of polyomavirus BK infected patients have been shown to be homozygous wild type AA genotype of TLR4-Asp299Gly (A896G) and CC genotype of TLR4- Thr399Ile (C1196T) polymorphisms. Homozygous mutant GG genotype of Asp299Gly (A896G) was found in 3 (2.1%) of the studied patients. Homozygous mutated TT genotype of Thr399Ile (C1196T) was found in only 5 (3.5%) of the liver recipients. There were no significant differences between homozygous wild type genotypes of studied TLR4 SNPs for liver transplant patients with or without polyomavirus BK infections. Significant association was also not found between homozygous mutated genotype of TLR4 SNPs for patients experiencing rejection episodes. However further completed studies on larger population and with longer follow-up are needed to confirm these results.