15 research outputs found
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Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry
Pharmacogenetics is the study of genetic variations that cause alterations in drug level, drug response and adverse drug reactions. SNPs found in CYP450 genes have the greatest genetic influences on interindividual variability in drug bioavailability. The polymorphic nature of these genes may modulate several enzyme levels that affect individual responses to pharmacological treatment. Among them, CYP3A4, CYP3A5, CYP2C9 and CYP2C19 isoforms of CYP450 enzymes are involved in the metabolism of many commonly prescribed drugs.
In this study, we would like to develop a CYP450 genotyping platform that could lead a complete definition of a patient's metabolic genotype in order to improve the clinical outcome of some drug treatments.
We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Sequenom) to develop a SNP genotyping method.
This MALDI-TOF-based multiplexing system allows the simultaneous and efficient genotyping of a set of CYP450 gene polymorphisms.
The multiple CYP450 gene testing achieved with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes
Entropy of human leukocyte antigen and killer-cell immunoglobulin-like receptor systems in immune-mediated disorders: A pilot study on multiple sclerosis
Entropy is a thermodynamic variable statistically correlated with the disorder of a system. The hypothesis that entropy can be used to identify potentially unhealthy conditions was first suggested by Schrödinger, one of the founding fathers of quantum mechanics. Shannon later defined entropy as the quantity of information stored in a system. Shannon's entropy has the advantage of being adaptable across a variety of disciplines, including genetic studies on complex immunogenetic systems such as the human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) systems
KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation
Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity
Risk of chronic rejection according to the presence or absence of specific recipient (r) KIR and donor (d) HLA ligand combinations.
<p>Risk of chronic rejection according to the presence or absence of specific recipient (r) KIR and donor (d) HLA ligand combinations.</p
KIR gene frequencies and KIR haplotypes in patients and 221 healthy controls.
<p>KIR gene frequencies and KIR haplotypes in patients and 221 healthy controls.</p
HLA Class I allele frequencies in cadaveric kidney donors and healthy controls.
<p>HLA Class I allele frequencies in cadaveric kidney donors and healthy controls.</p
Serum creatinine levels after transplantation in three groups of patients stratified according to the presence or absence of combinations of recipient (r) KIRs and donor (d) HLA ligands: rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4.
<p>Serum creatinine levels after transplantation in three groups of patients stratified according to the presence or absence of combinations of recipient (r) KIRs and donor (d) HLA ligands: rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4.</p
KIR-HLA ligand mismatches/matches in the 174 recipient/donor pairs.
<p>KIR-HLA ligand mismatches/matches in the 174 recipient/donor pairs.</p