TLR10 genotypes affect long-term graft function in tacrolimus-treated solid organ transplant recipients

Area of Science:

• Immunogenetics
• Transplantation Medicine
• Pharmacogenomics

Background:

• Tacrolimus (TAC) is a vital immunosuppressant post-transplantation.
• Genetic variations, particularly single nucleotide polymorphisms (SNPs), can influence drug efficacy and patient outcomes.
• The Toll-like receptor 10 (TLR10) gene's role in transplantation outcomes remains under investigation.

Purpose of the Study:

• To investigate the association between TLR10 gene SNPs and clinical outcomes in renal transplant patients treated with TAC.
• To validate these findings in liver transplant recipients.
• To identify specific TLR10 SNPs influencing graft function and TAC-related outcomes.

Main Methods:

• Genotyping of 19 TLR10 SNPs using matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS).
• Analysis of associations between recipient SNPs and clinical outcomes in 172 renal transplant patients.
• Confirmation study in 145 liver transplant recipient-donor pairs, examining recipient and donor SNP relationships with outcomes.

Main Results:

• Three TLR10 SNPs (rs28393318, rs11466655, rs11096957) significantly impacted renal transplant graft function.
• The rs11096957 SNP in liver transplant recipients was associated with altered total bilirubin (TBil) and direct bilirubin (DBil) levels.
• Significant association signals were found between TLR10 polymorphisms and clinical outcomes in TAC-treated transplant patients.

Conclusions:

• TLR10 gene polymorphisms are associated with clinical outcomes in renal and liver transplant patients receiving tacrolimus.
• The SNP rs11096957 in the TLR10 gene demonstrates a potential role in affecting graft function in both renal and liver transplantation.
• These findings highlight the importance of pharmacogenetic investigations of TLR10 in optimizing immunosuppressive therapy post-transplantation.