0000000000609628
AUTHOR
Juan Eduardo Megías
SNPs and taxane toxicity in breast cancer patients
Aim: In order to identify genetic variants associated with taxanes toxicity, a panel with 47 SNPs in 20 genes involved in taxane pathways was designed. Patients & methods: Genomic DNA of 113 breast cancer patients was analyzed (70 taking docetaxel, 43 taking paclitaxel). Results: Two SNPs associated with docetaxel toxicity were identified: CYP3A4*1B with infusion-related reactions; and ERCC1 Gln504Lys with mucositis (p ≤ 0.01). Regarding paclitaxel toxicity: CYP2C8 HapC and CYP2C8 rs1934951 were associated with anemia; and ERCC1 Gln504Lys with neuropathy (p ≤ 0.01). Conclusion: Genes involved in DNA repair mechanisms and reactive oxygen species levels influence taxane toxicity in cance…
Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation.
Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly hig…
Benefits of Ehl Factor VIII Replacement Therapy in Hemophilia: Observations on Coverage, Physical Activity and Phisiotherapy
Introduction: Prevention of haemophilic arthropathy and quality of life´s (QoL) improvement are still the main goals in the haemophilia community. Haemophilic arthropathy is the result of clinical and subclinical bleeding during everyday activities and/or traumatic situations. Prophylaxis with extended half-life (EHL) factor replacement therapy is understood as an improvement solution for factor VIII (FVIII) PK properties, as half-life (T1/2) and area under the curve (AUC), however few real world data are yet available. EHL improved pharmacokinetic (PK) properties might directly drive into a reduction of the bleeding risk during physical activity (both therapeutical or leisure) for a longer…
Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies
The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expre…