Title: Proton pump inhibitors therapy and cyp2c19 gene variability inCzech patients with gastroesophageal reflux disease: pilotstudy
Abstract: Proton pump inhibitors (PPIs) are a class of drugs used as the
first-line therapy to treat gastroesophageal reflux disease
(GERD). PPIs are metabolized mainly by cytochrome P450 2C19
(CYP2C19). The aim of the pilot study was to map the use of
these drugs in Czech patients with various degrees of GERD and
to analyze their individual variability in the gene encoding
the CYP2C19. A total of 280 subjects (mean age±standard
deviation: 46.23±13.11 years) were enrolled in the study: 95
patients with non-erosive reflux disease (NERD), 124 with
reflux esophagitis (RE) and 61 with Barrett's esophagus (BE) or
esophageal adenocarcinoma (EAC). The diagnosis was determined
on the basis of clinical symptoms such as heartburn (pyrosis)
and/or acid regurgitation; objectified with 24-h pH-metry,
esophagogastroduodenoscopy and manometry. The determination of
genotypes of two polymorphisms in the CYP2C19 gene (*17
rs12248560 and *2 rs4244285) was based on the principle of
real-time polymerase chain reaction with TaqMan assays. Almost
90% patients with GERD took one or more PPIs (omeprazole,
pantoprazole and/or lansoprazole). In addition, 37% patients
took some prokinetics and 16.4% patients had polypragmasy. The
results of haplogenotype analyses of the CYP2C19 gene
classified 36.8% patients into a group of extensive
metabolizers (*1*1/*1*1) or even ultrarapid metabolizers 37.2%
(*1*1/*1*17 and *1*1/*17*17); only smaller numbers of patients
were intermediate or poor metabolizers (17.1% or 1.4%,
respectively). We concluded that the most common
loss-of-function CYP2C19*2 and gain-of-function CYP2C19*17
variants should be examined in patients with GERD before PPI
pharmacotherapy is prescribed. Selection of adequate drugs and
their proper dosing may contribute to improve patients’s life
quality and prevent the progression to more severe GERD
conditions such as BE and EAC.
Publication Year: 2017
Publication Date: 2017-01-01
Language: en
Type: article
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