a 2022

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

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

Základní údaje

Originální název

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

Autoři

MLČŮCHOVÁ, Natálie (203 Česká republika), Břetislav LIPOVÝ (203 Česká republika), Zdeněk DANĚK (203 Česká republika), Lumír KUNOVSKÝ (203 Česká republika), Ondřej ZENDULKA (203 Česká republika), Ondřej PEŠ (203 Česká republika), Jan BÖHM (203 Česká republika), Radek KROUPA (203 Česká republika), Jitka VACULOVÁ (203 Česká republika), Tomáš GROLICH (203 Česká republika), Vladimír PROCHÁZKA (203 Česká republika), Vít NAVRÁTIL, Ondřej URBAN (203 Česká republika), Tomáš HARUŠTIAK, Robert LISCHKE (203 Česká republika), Lydie IZAKOVIČOVÁ HOLLÁ (203 Česká republika), Zdeněk KALA (203 Česká republika) a Petra BOŘILOVÁ LINHARTOVÁ (203 Česká republika, garant, domácí)

Vydání

Setkání biochemiků a molekulárních biologů, 2022, 2022

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14310/22:00127205

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

proton pump inhibitors; pharmacogenetics; ambivalent metabolizers; therapeutic drug monitoring
Změněno: 30. 3. 2023 13:42, Mgr. Terezie Slámová

Anotace

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.

Návaznosti

LM2018121, projekt VaV
Název: Výzkumná infrastruktura RECETOX (Akronym: RECETOX RI)
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, RECETOX RI
NU20-03-00126, projekt VaV
Název: Hostitelský mikrobiom ve vztahu k rozvoji Barrettova jícnu a adenokarcinomu jícnu
Investor: Ministerstvo zdravotnictví ČR, Hostitelský mikrobiom ve vztahu k rozvoji Barrettova jícnu a adenokarcinomu jícnu, Podprogram 1 - standardní