Toll-like receptor 4 and CD14 gene polymorphisms in Tunisian kidney transplantation

H Krichen1, Y Gorgi, T Dhaouadi

  • 1Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), University Tunis El Manar, Charles Nicolle Hospital, Tunis, Tunisia.

Transplantation Proceedings
|December 10, 2013
PubMed
Abstract

Insights

Single nucleotide polymorphisms (SNPs) in Toll-like receptor 4 (TLR4) and CD14 do not appear to influence acute rejection, chronic allograft nephropathy, or kidney transplant survival. Further research on gene expression is recommended for clarity.

Area of Science:

  • Immunogenetics
  • Transplantation Immunology
  • Molecular Biology

Background:

  • Graft loss after renal transplantation is often due to acute and chronic rejections.
  • Toll-like receptors (TLRs) activation is implicated in the loss of transplant tolerance.

Purpose of the Study:

  • To investigate the role of functional single nucleotide polymorphisms (SNPs) in TLR4 and its coreceptor CD14 in kidney transplantation.
  • To determine the impact of these SNPs on acute rejection (AR), chronic allograft nephropathy (CAN), and kidney graft survival.

Main Methods:

  • TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were genotyped in 209 kidney transplant recipients using PCR-RFLP.
  • AR and CAN were diagnosed by biopsy and scored using Banff criteria.

Main Results:

  • No significant associations were found between TLR4/CD14 genotypes/alleles and the occurrence of AR or CAN.
  • TLR4 and CD14 SNPs did not influence kidney graft survival, HLA compatibility, anti-HLA antibodies, or immunosuppression with MMF.
  • Incidence of post-transplantation infections, including CMV, was not affected by TLR4/CD14 SNPs.

Conclusions:

  • Functional SNPs of TLR4 (Asp299Gly) and CD14 (C/T -159) do not appear to be major factors in AR, CAN, or kidney graft survival.
  • Intragraft gene expression analysis of TLR4/CD14 via mRNA is suggested to elucidate their precise role in graft injuries.

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
81
Kidney Transplant I: Introduction01:28

Kidney Transplant I: Introduction

A kidney transplant is a surgical approach that involves replacing a non-functioning kidney with a healthy one from a donor. This procedure is often a treatment option for end-stage renal disease (ESRD) patients. The method requires careful recipient selection, including evaluating various medical and psychosocial factors. These criteria vary between transplant centers but generally include assessments of the patient's overall health, adherence to medical recommendations, and lifestyle...
827
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
159
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
189
Tissue Transplantation01:24

Tissue Transplantation

Tissue transplantation is a significant medical procedure involving the transfer of cells, tissues, or organs from a donor to a recipient, with the primary aim of restoring lost functions. This procedure is crucial in treating a broad spectrum of diseases, including kidney diseases, liver failure, heart disease, and certain types of cancers.
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...
1.4K
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
94