scholarly journals Prevalence of CYP2C19 polymorphism in Bogotá, Colombia: The first report of allele *17

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245401
Author(s):  
Azucena Arévalo-Galvis ◽  
William A. Otero-Regino ◽  
Gloria N. Ovalle-Celis ◽  
Eliana R. Rodríguez-Gómez ◽  
Alba A. Trespalacios-Rangel
Keyword(s):  
Plasma Concentrations ◽  
Poor Metabolizers ◽  
Gastric Ulcers ◽  
Cyp2c19 Polymorphism ◽  
Pcr Rflp ◽  
Different Types ◽  
Ultrarapid Metabolizers ◽  
Polymorphic Gene ◽  
Gerd Symptoms ◽  
Intermediate Metabolizers

Introduction Proton pump inhibitors (PPIs) are a group of drugs that are essential for the treatment of acid-related disorders, such as gastroesophageal reflux (GERD), dyspepsia, gastric ulcers and Helicobacter pylori (H. pylori) infection. PPIs such as omeprazole, esomeprazole, pantoprazole and lansoprazole are metabolized by the CYP2C19 enzyme, which is encoded by a polymorphic gene. Four polymorphisms have an impact on the speed of PPI metabolism: CYP2C19*1/*1 (extensive metabolizers), CYP2C19*2/*2 (intermediate metabolizers), CYP2C19*3/*3 (poor metabolizers) and CYP2C19*17/*17 (ultrarapid metabolizers). Extensive and ultrarapid metabolizers inactivate PPIs quickly, which consequently causes low plasma concentrations of PPIs, while intermediate or poor metabolizers have higher plasma concentrations of PPIs and, therefore, PPIs have greater therapeutic efficacy in individuals with these polymorphisms. Objective To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogotá, Colombia. Methods This observational study was conducted in Bogotá between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia, H. pylori infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche®), and PCR-RFLP was used to determine the presence of polymorphism *17. Results The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%). Conclusion The population studied consisted mainly of extensive and ultrarapid PPI metabolizers. These findings show that it is necessary to increase PPI doses in this group of subjects or to use PPIs that are not metabolized by CYP2C19 (rabeprazole). This is the first Colombian work to identify ultrarapid metabolizers.

Involvement of CYP2D6 and CYP2B6 on tramadol pharmacokinetics

2020 ◽  
Vol 21 (10) ◽  
pp. 663-675
Author(s):  
Miriam Saiz-Rodríguez ◽  
Dolores Ochoa ◽  
Manuel Román ◽  
Pablo Zubiaur ◽  
Dora Koller ◽  
...  
Keyword(s):  
Oral Dose ◽  
Healthy Volunteers ◽  
Sample Size ◽  
Genetic Variants ◽  
Plasma Levels ◽  
Small Sample Size ◽  
Plasma Concentrations ◽  
Small Sample ◽  
Ultrarapid Metabolizers ◽  
Intermediate Metabolizers

This study included 24 healthy volunteers who received a single 37.5 mg oral dose of tramadol. We analyzed 18 polymorphisms within CYP2D6, CYP2B6, CYP3A, COMT, ABCB1, SLC22A1 and OPRM1 genes by quantitative PCR, to study whether these polymorphisms affect its pharmacokinetics, pharmacodynamics and safety. CYP2D6 intermediate metabolizers (n = 6) showed higher tramadol plasma concentrations and lower clearance compared with normal and ultrarapid metabolizers. CYP2B6 G516T T/T (n = 2) genotype was also associated to higher tramadol plasma levels. No other polymorphism affected tramadol pharmacokinetics. Three volunteers experienced a prolonged QTc not associated with the genetic variants studied or altered phamacokinetic parameters. The correlation of CYP2B6 genotype with higher tramadol concentrations is remarkable since its influence on its elimination is also relevant and has been less studied to date. However, given our small sample size, it is important to interpret our results with caution.

scholarly journals CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 300
Author(s):  
Muhammad Miftahussurur ◽  
Dalla Doohan ◽  
Ari Fahrial Syam ◽  
Iswan Abbas Nusi ◽  
Phawinee Subsomwong ◽  
...  
Keyword(s):  
Proton Pump Inhibitor ◽  
Clinical Outcomes ◽  
Proton Pump ◽  
Poor Metabolizers ◽  
Wild Type Allele ◽  
Wild Type ◽  
Type Allele ◽  
Sydney System ◽  
Intermediate Metabolizers ◽  
Cyp2c19 Polymorphisms

CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

DNA Microarray Technology in the Clinical Environment: The AmpliChip CYP450 Test for CYP2D6 and CYP2C19 Genotyping

CNS Spectrums ◽  
2009 ◽  
Vol 14 (1) ◽  
pp. 19-35 ◽  
Author(s):  
Jose de Leon ◽  
Margaret T. Susce ◽  
Maria Johnson ◽  
Mike Hardin ◽  
Lorraine Maw ◽  
...  
Keyword(s):  
African Americans ◽  
Dna Microarray ◽  
Dna Sequences ◽  
Psychiatric Patients ◽  
Poor Metabolizers ◽  
Microarray Technology ◽  
Clinical Environment ◽  
State Hospitals ◽  
Cyp2c19 Gene ◽  
Ultrarapid Metabolizers

ABSTRACTIntroduction: An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology.Methods: A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype.Results: In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.1%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%).Conclusion: We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.

Postoperative plasma concentrations of procalcitonin after different types of surgery

1998 ◽  
Vol 24 (7) ◽  
pp. 680-684 ◽  
Author(s):  
M. Meisner ◽  
K. Tschaikowsky ◽  
A. Hutzler ◽  
J. Schüttler ◽  
C. Schick
Keyword(s):  
Plasma Concentrations ◽  
Different Types

Training-induced energy balance mismatch in Standardbred mares

2006 ◽  
Vol 3 (2) ◽  
pp. 73-82 ◽  
Author(s):  
ME Gordon ◽  
KH McKeever ◽  
S Bokman ◽  
CL Betros ◽  
HC Manso-Filho ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Gastric Ulcers ◽  
Adaptation Period ◽  
Maximal Heart Rate ◽  
Exercise Tests ◽  
Percentage Body Fat ◽  
Warm Up ◽  
Westervelt Equation ◽  
Plasma Leptin ◽  
Over Time

AbstractThis study tested the hypothesis that exercise training would alter feed intake (FI), body composition (BC) and plasma concentrations of active ghrelin, leptin, cortisol, insulin and glucose. Eight Standardbred mares (12±2 years, 509±36 kg body weight (BW), mean±SD) were trained (EX) in an equine Equi-ciser (initially 3 days per week at 60% maximal heart rate (HRmax) for 20 min and gradually increased to 5 days per week at 70% HRmax for 30 min, with a 10-min warm-up and 10-min cool-down period at the walk). Six mares (12±2 years, 537±45 kg) served as non-exercise controls (CON). All mares were unfit and had not been subjected to conditioning for 3 years before the experiment. Pre- and post-training incremental exercise tests (GXT) were run to determine HRmax and maximal oxygen uptake (VO2max). A total mixed ration (TMR) of hay cubes was fed free choice for 16 h day-1 with the primary experiment following a 6-week diet adaptation period. Mares' FI was measured daily and reported in grams per kilogram BW of feed eaten per week. Changes in BC were assessed using BW (electronic scale) and percentage fat calculated using rump fat thickness and the Westervelt equation. Blood samples were taken every 2 weeks at 15:25, before mares were given their allotment of hay cubes on a day when they did not exercise, to measure plasma hormone and glucose concentrations. Gastroscopy for gastric ulcers was performed before, during and after the trial. VO2max increased by 7.0% (P<0.03) in EX, but did not change (P>0.05) in CON. FI decreased (P<0.001) in both groups, but was only different (P<0.02) between EX and CON at week 3. Digestible energy (DE) intake (Mcal day-1) was initially higher (P<0.001) than calculated DE requirements in EX. However, over time, DE only matched and then fell below (P<0.03) the DE intake required for training. In CON horses, DE intake was higher (P<0.001) than calculated requirements. BW and percentage body fat increased (P<0.001) over time in EX and CON. Plasma leptin concentration increased (P<0.001) over time in both groups, but was 60% higher (P<0.04) in CON compared to EX at weeks 4–8. There were no differences (P>0.05) in active ghrelin, glucose, insulin or cortisol between the groups and over time. Five out of seven EX mares developed gastric ulcers. No CON mares developed gastric ulcers. Training was associated with changes in plasma leptin concentration, an increased incidence of gastric ulcers and a disruption of the balance between required DE and actual intake.

Haplotypes of (−794(CATT)5–8/−173G>C) MIF gene polymorphisms and its soluble levels in basal cell carcinoma in western Mexican population

2020 ◽  
Vol 69 (1) ◽  
pp. 41-46
Author(s):  
Elizabeth Guevara-Gutiérrez ◽  
María José Castro-Jonguitud ◽  
Susana Elizabeth De la Torre-Flores ◽  
José Francisco Muñoz-Valle ◽  
Alberto Tlacuilo-Parra ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Gene Polymorphisms ◽  
Macrophage Migration Inhibitory Factor ◽  
Serum Levels ◽  
Study Groups ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Different Types

Basal cell carcinoma (BCC) is the most common dermatological neoplasms in Caucasian populations. In Mexico, a prevalence of 3.9 per 1000 habitants is estimated. Recently, the macrophage migration inhibitory factor (MIF) has been related to different types of cancer. Therefore, this study aimed to investigate the genetic association of haplotypes of [-794(CATT)5-8/-173G>C]MIF gene polymorphisms and its soluble levels in BCC. A total of 360 individuals were recruited for the study, that is, 180 of the total amounts were patients with BCC histologically confirmed and the remaining 180 individuals were identified as control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP (restriction fragment length polymorphism), and MIF serum levels were measured by ELISA kit. A borderline difference was found between the 55 genotype and the susceptibility to BCC (5.6% vs 1.7% in BCC and CS, respectively, OR=3.7 and p=0.04). Furthermore, the haplotype 7G showed a significant association with BCC (p=0.02, OR=1.99). Concerning MIF soluble levels, patients with BCC showed a media of 2.1 ng/mL and CS showed 4.4 ng/mL, the comparison between groups was significant (p<0.01). Our findings suggest that the 55 genotype and the haplotype 7G are associated with the susceptibility to BCC; furthermore, a significant difference was found between MIF soluble levels in both study groups.

Effect of PK-guided tamoxifen dose escalation on endoxifen serum concentrations in CYP2D6 intermediate and poor metabolizers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 595-595
Author(s):  
Frans Opdam ◽  
Vincent O. Dezentje ◽  
Jan den Hartigh ◽  
Henk-jan Guchelaar ◽  
Trees Hessing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Dose Escalation ◽  
Poor Metabolizers ◽  
Tamoxifen Treatment ◽  
Extensive Metabolizers ◽  
Breast Cancer Patients ◽  
One Step ◽  
Intermediate Metabolizers

595 Background: Breast cancer patients with absent or reduced CYP2D6 activity may benefit less from tamoxifen treatment because of impaired biotransformation to the active metabolite endoxifen. We investigated whether a temporary one-step dose escalation of tamoxifen in CYP2D6 poor (PM) and intermediate metabolizers (IM) could increase endoxifen serum concentration to a similar level observed in CYP2D6 extensive metabolizers (EM) without increasing toxicity. Methods: From a prospective study population of early breast cancer patients using tamoxifen, 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during two months. The escalation dose (120 mg maximum) was calculated by multiplying the individual’s endoxifen level divided by the median endoxifen concentration (33.7 nM) observed in CYP2D6 extensive metabolizers by 20 mg. Toxicity was assessed and all patients returned to the standard dose of 20 mg after two months. Results: Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (PMs: from 8.0 nM to 27.3 nM, p<0.001; IMs: from 17.8 nM to 30.3 nM, p=0.002) without increasing side effects. In intermediate but not in poor metabolizers dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers using tamoxifen 20 mg once daily (33.7 nM). Conclusions: CYP2D6 genotype and endoxifen guided tamoxifen dose escalation increased endoxifen concentrations without increasing short term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long term toxic effects is uncertain and needs to be explored. Clinical trial information: NTR1509.

Plasma concentrations of alpha-tocopherol and urate in patients with different types of cancer

2001 ◽  
Vol 26 (4) ◽  
pp. 265-270 ◽  
Author(s):  
C. Abiaka ◽  
F. Al-Awadi ◽  
S. Gulshan ◽  
H. Al-Sayer ◽  
A. Behbehani ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Alpha Tocopherol ◽  
Different Types

scholarly journals Studying of cyp2c19*2, *3 and *17 polymorphism in Vietnamese patients with coronary artery disease

2020 ◽  
Vol 18 (1) ◽  
pp. 41-48
Author(s):  
Nguyen Hai Ha ◽  
Le Thi Bich Thao ◽  
Nguyen Thi Thanh Hoa ◽  
Le Thi Thu Hien
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Restriction Enzymes ◽  
Metabolic Phenotype ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Cyp2c19 Gene ◽  
Ultrarapid Metabolizers ◽  
Coronary Syndromes ◽  
Artery Disease

Coronary artery disease is the most common type of cardiovascular disease, due to the accumulation of atherosclerotic plaque inside the arterial wall which leads to block blood supply to the heart muscle. A number of clinical trials have demonstrated that Clopidogrel is able to inhibit platelet aggregation in patients with acute coronary syndromes, reduce mortality and cardiovascular events. However, the antiplatelet effectiveness of Clopidogrel significantly depends on CYP2C19 genotypes. Therefore, the aim of this study was to identify the CYP2C19*2, *3 and allele frequencies in Vietnamese coronary artery patients by using PCR-RFLP method. Total genomic DNA were extracted from peripheral blood of 96 patients diagnosed with coronary artery disease. Thereafter, single nucleotide polymorphism sites in the CYP2C19 gene were identified by PCR with specific primers. The amplified products were then digested by restriction enzymes SmaI, BamHI, and MnlI, respectively. The results showed that the proportion of heterozygous individuals for CYP2C19*2 (c. 681G>A, rs4244285), CYP2C19*3 (c. 636G>A, rs4986893), and CYP2C19*17 (g. -3402C>T, rs11188072) accounted for 39.58%, 6.25%, and 2.08%, respectively. Among 96 subjects, 41.67% of patients were predicted for intermediate metabolic phenotype CYP2C19*1/*2 (37.50%) and CYP2C19*1/*3 (4.17%). Approximately 10.42% of total patients represented poor metabolizers in which 8.34% had two copies of the same allele *2/*2 and 2.08% had *2/*3 genotype. Particularly, two individuals (2.08%) detected with CYP2C19*1/*17 genotype were able to increase CYP2C19 activity (ultrarapid metabolizers). The results of this study generate a foundation for introducing individualized antiplatelet therapy in Vietnam based on genetic testing.

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