Frequency of genetic polymorphism for adrenergic receptor beta and cytochrome p450 2D6 enzyme and effects on the tolerability to Beta-blocker therapy in heart failure with reduced ejection fraction patients: Beta GenTURK Study

2016 ◽  
Author(s):  
Mehdi Zoghi
Keyword(s):  
Heart Failure ◽  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Ejection Fraction ◽  
Adrenergic Receptor ◽  
Cytochrome P450 2D6 ◽  
Blocker Therapy ◽  
Reduced Ejection Fraction ◽  
P450 2D6 ◽  
Receptor Beta

scholarly journals α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction

2019 ◽  
Vol 316 (5) ◽  
pp. R512-R524 ◽  
Author(s):  
Zachary Barrett-O’Keefe ◽  
Joshua F. Lee ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Melissa A. H. Witman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Adrenergic Receptor ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow ◽  
Reduced Ejection Fraction ◽  
Leg Blood Flow ◽  
Related Increase

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (−15 ± 7%) compared with controls (−36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (−12 ± 4, −10 ± 4, and −9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (−8 ± 5, −10 ± 3, and −14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.

Genetic Polymorphism of Cytochrome P450 2D6*4 and 2D6*5 in an Adult Population Sample from Costa Rica

2016 ◽  
Vol 16 (1-2) ◽  
pp. 10-15
Author(s):  
Chaverri-Fernández José Miguel ◽  
Ortiz-Ureña Angie ◽  
Díaz-Madriz José Pablo ◽  
Alvarado-Leitón Jeimy ◽  
García-Chaves, Sergio ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Costa Rica ◽  
Adult Population ◽  
Population Sample ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

scholarly journals Could Cytochrome P450 2D6, 3A4 and 3A5 Polymorphisms Explain the Variability in Clinical Response to Clomiphene Citrate of Anovulatory PCOS Women?

2021 ◽  
Vol 12 ◽  
Author(s):  
Camille Robin ◽  
Benjamin Hennart ◽  
Franck Broly ◽  
Philippine Gruchala ◽  
Geoffroy Robin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Clinical Response ◽  
Cytochromes P450 ◽  
Clomiphene Citrate ◽  
Weighted Kappa ◽  
Ovarian Response ◽  
Kappa Coefficient ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

IntroductionCytochrome P450 2D6, 3A4 and 3A5 are involved in the metabolism of many drugs. These enzymes have a genetic polymorphism responsible for different metabolic phenotypes. They play a role in the metabolism of clomiphene citrate (CC), which is used to induce ovulation. Response to CC treatment is variable, and no predictive factors have thus far been identified.ObjectiveTo study a possible link between the cytochrome P450 2D6, 3A4 and 3A5 polymorphisms and clinical response to CC.Study DesignSeventy-seven women with anovulatory Polycystic Ovarian Syndrome (PCOS) treated with CC were included which determined their cytochrome P450 2D6, 3A4 and 3A5 genotypes and used the results to predict ovarian response to this drug. Predicted responses based on the cytochrome genotypes were compared with the observed clinical responses using the calculation of a weighted Kappa coefficient.Main Outcome MeasuresNumber of dominant follicles assessed by ultrasound at the end of the follicular phase and confirmation of ovulation by blood progesterone assay in the luteal phase.ResultsConcordance between the predicted and observed responses for the combination of the three cytochromes was 36.71%, with a negative Kappa coefficient (K = -0.0240), which corresponds to a major disagreement. Similarly, for predictions based on the cytochrome P450 2D6 genotype alone, only 39.24% of predictions were verified (coefficient K = -0.0609).ConclusionThe genetic polymorphism of cytochromes P450 2D6, 3A4 and 3A5 does not appear to influence clinical response to CC used to induce ovulation in anovulatory PCOS women.

scholarly journals Breast cancer: Role of pharmacogenetics in tamoxifen therapy

2016 ◽  
Vol 1 (1) ◽  
pp. 10
Author(s):  
Smriti Mishra ◽  
Manish Manish
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Clinical Outcome ◽  
Tamoxifen Therapy ◽  
Uridine Diphosphate ◽  
Cytochrome P450 2D6 ◽  
Cytochrome P450 3A ◽  
P450 2D6

<p><span>The role of pharmacogenetics in the personalization of tamoxifen therapy has relevance in the management of breast cancer. Since Tamoxifen is a pro-drug, genetic polymorphism in Phase I and Phase II drug metabolizing enzymes involved in the bioconversion of tamoxifen to therapeutically active metabolites is critical in determining therapeutic efficacy and adverse drug reactions of the therapy in breast cancer patients. In this review, the role of pharmacogenetics in the personalization of tamoxifen therapy has been discussed. Since, metabolism of tamoxifen by Cytochrome P450 2D6 is significant in determining the therapeutic efficacy of the drug, most of the clinical evidence on tamoxifen pharmacogenetics have been correlated with cytochrome p450 2D6 genetic polymorphism. However, there is discordance in the clinical data, and one of the reasons is the incomplete analysis of all the alleles of cytochrome p450 2D6. International Tamoxifen Pharmacogenomics Consortium has been formed to assess   the discordance. There are also clinical evidences associating genetic polymorphism in cytochrome P450 3A, 2C9, 2C19, Uridine diphosphate –glucuronosyltransferases and Sulfotransferases with clinical outcome of tamoxifen therapy. However, associations of genetic polymorphism in cytochrome P450 3A, 2C9, 2C19, Uridine diphosphate –glucuronosyltransferases and Sulfotransferases with clinical outcome in populations of different ethnicity are unexplored. Evidences on  the association of genetic polymorphisms and the clinical outcome have been summarized in the Table.  Since cost, statistically significant sample population size, labor and ethical issues are the major concerns of a pharmacogenetic investigation; the significance of bottom-up approach in pharmacogenetics has been discussed.</span></p>

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