Pharmacogenetics of proton pump inhibitors and prevalence of
the CYP2C19*2 and *17 variants in the Central European
population

a 2022

Pharmacogenetics of proton pump inhibitors and prevalence of the CYP2C192 and 17 variants in the Central European population

MLČŮCHOVÁ, Natálie, Břetislav LIPOVÝ, Zdeněk DANĚK, Lumír KUNOVSKÝ, Ondřej ZENDULKA et. al.

Basic information

Original name

Pharmacogenetics of proton pump inhibitors and prevalence of the CYP2C19*2 and *17 variants in the Central European population

Authors

MLČŮCHOVÁ, Natálie (203 Czech Republic), Břetislav LIPOVÝ (203 Czech Republic), Zdeněk DANĚK (203 Czech Republic), Lumír KUNOVSKÝ (203 Czech Republic), Ondřej ZENDULKA (203 Czech Republic), Ondřej PEŠ (203 Czech Republic), Jan BÖHM (203 Czech Republic), Radek KROUPA (203 Czech Republic), Jitka VACULOVÁ (203 Czech Republic), Tomáš GROLICH (203 Czech Republic), Vladimír PROCHÁZKA (203 Czech Republic), Vít NAVRÁTIL, Ondřej URBAN (203 Czech Republic), Tomáš HARUŠTIAK, Robert LISCHKE (203 Czech Republic), Lydie IZAKOVIČOVÁ HOLLÁ (203 Czech Republic), Zdeněk KALA (203 Czech Republic) and Petra BOŘILOVÁ LINHARTOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Setkání biochemiků a molekulárních biologů, 2022, 2022

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14310/22:00127205

Organization unit

Faculty of Science

Keywords in English

proton pump inhibitors; pharmacogenetics; ambivalent metabolizers; therapeutic drug monitoring

Změněno: 30/3/2023 13:42, Mgr. Terezie Slámová

Abstract

V originále

Objective: Proton pump inhibitors (PPIs) are administered to patients with acid peptic disorders, such as gastroesophageal reflux disease. The efficiency of treatment by most PPIs largely depends on the cytochrome P450 2C19 (CYP2C19). The activity of this enzyme, genetically determined by the CYP2C19*2 (rs4244285) and CYP2C19*17 (rs12248560) allele variants, can be used to predict the efficacy of this enzyme and, thus, the rate of PPI metabolization. Nevertheless, the phenotype of a novel group of „ambivalent“ metabolizers with both the CYP2C19*2 and CYP2C19*17 variants is unknown. This work aims to evaluate the distribution of metabolizers, mainly focusing on the „ambivalent“ metabolizers in the Central European population and to determine their CYP2C19 metabolic activity. Methods: 545 patients were included in our study; of these, 58 used lansoprazole (Lanzul, 30 mg). Blood samples were drawn to 9 ml K3EDTA and genomic DNA was isolated. Genotypes of two variants CYP2C19*2 and *17 were determined using qPCR and haplogenotypes were evaluated. In patients using lansoprazole, blood samples were taken 3 hours after oral administration of the drug, plasma was transferred into 1.5 ml tubes immediately and stored at -80°C. A therapeutic drug monitoring approach was used to determine the patient‘s phenotype. Plasma concentrations of lansoprazole and its metabolite 5-hydroxylansoprazole were measured by liquid chromatography with absorbance or mass spectrometry detection. Results: Minor allele frequencies in the studied population were 14.7% for the CYP2C19*2 and 25.7% for the CYP2C19*17 variants. Individuals without any variant allele, known as extensive metabolizers (*1*1/*1*1; 36.2%), were the most common. Ultrarapid and rapid metabolizers (*1*17/*1*1 and *17*17/*1*1) were represented by 36.0%. Intermediate metabolizers were less common (*1*1/*1*2; 18.2%) and only 1.5% of participants were poor metabolizers (*1*1/*2*2). 8.3% of participants were shown to be „ambivalent“ metabolizers (*1*17/*1*2), a group whose phenotype was not known. Based on the metabolization rate, the phenotype of ambivalent metabolizers resembled that of extensive metabolizers evaluated in this study. There was no association between concentration of lansoprazole/5-hydroxylansoprazole and metabolic ratio/sex/smoking/alcohol consumption (p > 0.05). Conclusions: This study revealed that ambivalent metabolizers are relatively common in the Central European population and should be considered when discussing the rate of metabolization of PPIs. Their phenotype seems to be close to that of extensive metabolizers, which can play an important role in personalized pharmacotherapy by PPIs in these patients.

Links

LM2018121, research and development project

Name: Výzkumná infrastruktura RECETOX (Acronym: RECETOX RI)

Investor: Ministry of Education, Youth and Sports of the CR, RECETOX RI

NU20-03-00126, research and development project

Name: Hostitelský mikrobiom ve vztahu k rozvoji Barrettova jícnu a adenokarcinomu jícnu

Investor: Ministry of Health of the CR, Host microbiome in relation to Barrett ́s esophagus and esophageal adenocarcinoma development, Subprogram 1 - standard

Citovat

MLČŮCHOVÁ, Natálie, Břetislav LIPOVÝ, Zdeněk DANĚK, Lumír KUNOVSKÝ, Ondřej ZENDULKA, Ondřej PEŠ, Jan BÖHM, Radek KROUPA, Jitka VACULOVÁ, Tomáš GROLICH, Vladimír PROCHÁZKA, Vít NAVRÁTIL, Ondřej URBAN, Tomáš HARUŠTIAK, Robert LISCHKE, Lydie IZAKOVIČOVÁ HOLLÁ, Zdeněk KALA and Petra BOŘILOVÁ LINHARTOVÁ. Pharmacogenetics of proton pump inhibitors and prevalence of the CYP2C19*2 and *17 variants in the Central European population. In Setkání biochemiků a molekulárních biologů, 2022. 2022.

@proceedings{2233292,
   author = {Mlčůchová, Natálie and Lipový, Břetislav and Daněk, Zdeněk and Kunovský, Lumír and Zendulka, Ondřej and Peš, Ondřej and Böhm, Jan and Kroupa, Radek and Vaculová, Jitka and Grolich, Tomáš and Procházka, Vladimír and Navrátil, Vít and Urban, Ondřej and Haruštiak, Tomáš and Lischke, Robert and Izakovičová Hollá, Lydie and Kala, Zdeněk and Bořilová Linhartová, Petra},
   booktitle = {Setkání biochemiků a molekulárních biologů, 2022},
   keywords = {proton pump inhibitors; pharmacogenetics; ambivalent metabolizers; therapeutic drug monitoring},
   language = {eng},
   title = {Pharmacogenetics of proton pump inhibitors and prevalence of the CYP2C19*2 and *17 variants in the Central European population},
   year = {2022}
}

TY  - CONF
ID  - 2233292
AU  - Mlčůchová, Natálie - Lipový, Břetislav - Daněk, Zdeněk - Kunovský, Lumír - Zendulka, Ondřej - Peš, Ondřej - Böhm, Jan - Kroupa, Radek - Vaculová, Jitka - Grolich, Tomáš - Procházka, Vladimír - Navrátil, Vít - Urban, Ondřej - Haruštiak, Tomáš - Lischke, Robert - Izakovičová Hollá, Lydie - Kala, Zdeněk - Bořilová Linhartová, Petra
PY  - 2022
TI  - Pharmacogenetics of proton pump inhibitors and prevalence of the CYP2C19*2 and *17 variants in the Central European population
KW  - proton pump inhibitors
KW  - pharmacogenetics
KW  - ambivalent metabolizers
KW  - therapeutic drug monitoring
N2  - Objective: Proton pump inhibitors (PPIs) are administered to patients with acid peptic disorders, such as gastroesophageal reflux disease. The efficiency of treatment by most PPIs largely depends on the cytochrome P450 2C19 (CYP2C19). The activity of this enzyme, genetically determined by the CYP2C19*2 (rs4244285) and CYP2C19*17 (rs12248560) allele variants, can be used to predict the efficacy of this enzyme and, thus, the rate of PPI metabolization. Nevertheless, the phenotype of a novel group of „ambivalent“ metabolizers with both the CYP2C19*2 and CYP2C19*17 variants is unknown. This work aims to evaluate the distribution of metabolizers, mainly focusing on the „ambivalent“ metabolizers in the Central European population and to determine their CYP2C19 metabolic activity. Methods: 545 patients were included in our study; of these, 58 used lansoprazole (Lanzul, 30 mg). Blood samples were drawn to 9 ml K3EDTA and genomic DNA was isolated. Genotypes of two variants CYP2C19*2 and *17 were determined using qPCR and haplogenotypes were evaluated. In patients using lansoprazole, blood samples were taken 3 hours after oral administration of the drug, plasma was transferred into 1.5 ml tubes immediately and stored at -80°C. A therapeutic drug monitoring approach was used to determine the patient‘s phenotype. Plasma concentrations of lansoprazole and its metabolite 5-hydroxylansoprazole were measured by liquid chromatography with absorbance or mass spectrometry detection. Results: Minor allele frequencies in the studied population were 14.7% for the CYP2C19*2 and 25.7% for the CYP2C19*17 variants. Individuals without any variant allele, known as extensive metabolizers (*1*1/*1*1; 36.2%), were the most common. Ultrarapid and rapid metabolizers (*1*17/*1*1 and *17*17/*1*1) were represented by 36.0%. Intermediate metabolizers were less common (*1*1/*1*2; 18.2%) and only 1.5% of participants were poor metabolizers (*1*1/*2*2). 8.3% of participants were shown to be „ambivalent“ metabolizers (*1*17/*1*2), a group whose phenotype was not known. Based on the metabolization rate, the phenotype of ambivalent metabolizers resembled that of extensive metabolizers evaluated in this study. There was no association between concentration of lansoprazole/5-hydroxylansoprazole and metabolic ratio/sex/smoking/alcohol consumption (p > 0.05). Conclusions: This study revealed that ambivalent metabolizers are relatively common in the Central European population and should be considered when discussing the rate of metabolization of PPIs. Their phenotype seems to be close to that of extensive metabolizers, which can play an important role in personalized pharmacotherapy by PPIs in these patients.
ER  -

MLČŮCHOVÁ, Natálie, Břetislav LIPOVÝ, Zdeněk DANĚK, Lumír KUNOVSKÝ, Ondřej ZENDULKA, Ondřej PEŠ, Jan BÖHM, Radek KROUPA, Jitka VACULOVÁ, Tomáš GROLICH, Vladimír PROCHÁZKA, Vít NAVRÁTIL, Ondřej URBAN, Tomáš HARUŠTIAK, Robert LISCHKE, Lydie IZAKOVIČOVÁ HOLLÁ, Zdeněk KALA and Petra BOŘILOVÁ LINHARTOVÁ. Pharmacogenetics of proton pump inhibitors and prevalence of the CYP2C19*2 and *17 variants in the Central European population. In \textit{Setkání biochemiků a molekulárních biologů, 2022}. 2022.

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