Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
5-Year IF – 2.0, IF – 1.9, JCI (2024) – 0.43
Scopus CiteScore – 4.3
Q1 in SJR 2024, SJR score – 0.598, H-index: 49 (SJR)
ICV – 161.00; MNiSW – 70 pts
Initial editorial assessment and first decision within 24 h

ISSN 1899–5276 (print), ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2011, vol. 20, nr 1, January-February, p. 65–69

Publication type: original article

Language: English

CYP2C19 Polymorphism in Patients with Gastroesophageal Reflux Disease – a Pilot Study

Polimorfizm CYP2C19 u pacjentów z chorobą refluksową przełyku – badanie wstępne

Elżbieta Poniewierka1,, Katarzyna Neubauer2,, Radosław Kempiński3,, Marta Strutyńska-Karpińska3,, Anna Sadakierska-Chudy4,

1 Department of Gastroenterology and Hepatology, Division of Dietetics, Wroclaw Medical University, Poland

2 Department and Clinic of Gastroenterology and Hepatology, Wroclaw Medical University, Poland

3 Department and Clinic of Gastrointestinal and General Surgery, Wroclaw Medical University, Poland

4 Molecular Techniques Unit, Wroclaw Medical University, Poland, Institute of Pharmacology, Polish Academy of Sciences

Abstract

Background. Gastroesophageal reflux disease (GERD) is a disease of modern civilization whose symptoms occur in 5–10% of individuals living in Western countries. Proton pump inhibitors (PPIs) are the basis of the medical treatment of GERD. PPIs are metabolized with the system of enzymes of cytochrome P450. Polymorphism of the isoenzymes comprising this system determines the different speeds of the metabolism of the drugs.
Objectives. The aim of the study was the analysis of CYP2C19 polymorphism in GERD patients in relation to the presence of GERD complications.
Material and Methods. The study group consisted of 40 patients hospitalized in the Department of Gastroenterology and Hepatology of Wroclaw Medical University with a diagnosis of GERD and 17 patients treated surgically in the Clinic of Gastrointestinal and General Surgery of Wroclaw Medical University due to GERD complications. Two SNP-type polymorphisms in gene CYP2C19 were studied with the PCR-RFLP (polymerase chain reaction, restriction fragment length polymorphism) method.
Results. Most of the patients were found to belong to the phenotype of extensive metabolizers (EM). Genotypes and frequency of the alleles of polymorphism 681G→A in gene CYP2C19 in GERD patient groups with and without complications are shown in table 2.
Conclusion. Most of the patients with uncomplicated GERD belong to the phenotype of extensive metabolizers (EM). Our results do not suggest that the polymorphism of gene CYP2C19 plays a role in the development of severe GERD complications.

Streszczenie

Wprowadzenie. Choroba refluksowa przełyku jest chorobą cywilizacyjną, której objawy występują u 5–10% mieszkańców krajów zachodnich. Podstawą terapii zachowawczej GERD są inhibitory pompy protonowej (i.p.p.). W metabolizmie tych leków bierze udział system enzymów cytochromu P-450. Polimorfizm izoenzymów wchodzących w skład systemu warunkuje różną szybkość metabolizmu leków.
Cel pracy. Analiza polimorfizmu genu CYP2C19 u pacjentów z GERD.
Materiał i metody. Grupę badaną tworzyło 40 pacjentów hospitalizowanych w Klinice Gastroenterologii i Hepatologii AM we Wrocławiu z rozpoznaniem GERD oraz 17 pacjentów leczonych chirurgicznie w Klinice Chirurgii Przewodu Pokarmowego i Chirurgii Ogólnej AM we Wrocławiu z powodu powikłań GERD. Do badania dwóch polimorfizmów typu SNP w genie CYP2C19 wykorzystano metodę PCR-RFLP.
Wyniki. Większość pacjentów z niepowikłaną chorobą refluksową przełyku należy do grupy osób szybko metabolizujących. Rozkład genotypów i częstości alleli polimorfizmu 681G→A w genie CYP2C19 w grupie pacjentów z GERD bez powikłań i u pacjentów leczonych chirurgicznie z powodu powikłań GERD przedstawiono w tabeli 2.
Wnioski. Większość pacjentów z niepowikłaną chorobą refluksową przełyku należy do osób szybko metabolizujących. Uzyskane wyniki nie przemawiają za udziałem polimorfizmu genu CYP2C19 w rozwoju ciężkich powikłań choroby.

Key words

CYP2C19, gastroesophageal reflux disease, proton pump inhibitors

Słowa kluczowe

CYP2C19, choroba refluksowa przełyku, inhibitory pompy protonowej

References (17)

  1. Van der Wende J, Steijns LS: Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem 1999, 36, 722–729.
  2. Evans WE, Relling MV: Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999, 286, 487–491.
  3. Klotz U, Schwab M, Treiber G: CYP2C19 polymorphism and proton pump inhibitors. Basic Clin Pharmacol Toxicol 2004, 95, 2–8.
  4. Desta Z, Zhao X, Shin JG, Flockhart DA: Clinical significance of the cytochrome P450 CYP2C19 genetic polymorphism. Clin Pharmacokinet 2002, 41, 913–958.
  5. Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmoller J: Pharmacogenetics of antidepressants and antipsychotic: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004, 9, 442–473.
  6. de Morais SMF, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA: The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 1994, 269, 15419–15422.
  7. Zand N, Tajik N, Hoormand M, Moghaddam AS, Milanian I: Allele frequency of CYP2C19 gene polymorphisms in healthy Iranian population. IJPT 2005, 4, 124–127.
  8. Furuta T, Shirai N, Sugimoto M, Ohashi K, Ishizaki T: Pharmacogenomics of proton pump inhibitors. Pharmacogenomics 2004, 5, 181–202.
  9. Furuta T, Ohashi K, Kamata T, Takashima M, Kosuge K, Kawasami T et al.: Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer. Ann Intern Med 1998, 129, 1027–1030.
  10. Furtura T, Shari N, Watanabe F, Honda S, Takeuchi K, Iida T et al.: Effect of cytochrome P450 2C19 genetic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther 2002, 72, 453–460.
  11. Kawamura M, Ohara S, Koine T, Iijima K, Suzuki J, Kaaba S et al.: The effects of lansoprazole on erosie reflux oesophagitis are influence by CYP2C19 polymorphisms. Aliment Pharmacol Ther 2003, 17, 965–973.
  12. Saitoh T, Fukushima Y, Otsuka H, Hirakawa J, Mori H, Asano T, Ishikawa T, Katsube T, Ogawa K, Ohkawa S: Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers. Aliment Pharmacol Ther 2002, 16, 1811–1817.
  13. Sim SS, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, Ingelman-Sundberg M: A common novel VYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 2006, 79, 103–113.
  14. Klotz U: Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. Int J Clin Pharmacol Ther 2006, 44, 297–302.
  15. Tseng PH, Lee YC, Chiu HM, Wang HP, Lin JT, Wu MS: A comparative study of proton-pump inhibitor tests for Chinese reflux patients in relation to the CYP2C19 genotypes. J Clin Gastroenterol 2009, 43, 920–925.
  16. Lee YC, Lin JT, Wang HP, Chiu HM, Wu MS: Influence of cytochrome P450 2C19 genetic polymorphism and dosage of rabeprazole on accuracy of proton-pump inhibitor testing in Chinese patients with gastroesophageal reflux disease. J Gastroenterol Hepatol 2007, 22, 1286–1292.
  17. Saitoh T, Otsuka H, Kawasaki T, Endo H, Iga D, Tomimatsu M, Fukushima Y, Katsube T, Ogawa K, Otsuka K: Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during proton pump inhibitor maintenance therapy. Hepatogastroenterology 2009, 56, 703–706.
© Wroclaw Medical University