Clinical and pharmacogenetic features of patients with upper gastrointestinal lesions at a multidisciplinary hospital: the role of nonsteroidal anti-inflammatory drugs

Author:

Denisenko Natalia P.1ORCID,Zhiryakova Anna S.23ORCID,Sychev Ivan V.1ORCID,Kryukov Alexander V.23ORCID,Tuchkova Svetlana N.1ORCID,Vakulenko Olga Y.4ORCID,Averkov Oleg V.5ORCID,Vechorko Valery I.6ORCID,Mirzaev Karin B.1ORCID,Sychev Dmitry A.2ORCID

Affiliation:

1. Research Institute of Molecular and Personalized Medicine , 442138 Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation

2. Department of Clinical Pharmacology and Therapeutics named after Academician B.E. Votchal , Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation

3. Department of Clinical pharmacology , Municipal Clinical Hospital No. 15 named after O.M. Filatov , Moscow , Russian Federation

4. Clinical Diagnostic Department , Municipal Clinical Hospital No. 15 named after O.M. Filatov , Moscow , Russian Federation

5. The Regional Vascular Center , Municipal Clinical Hospital No. 15 named after O.M. Filatov , Moscow , Russian Federation

6. Municipal Clinical Hospital No. 15 named after O.M. Filatov , Moscow , Russian Federation

Abstract

Abstract Objectives Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, but their use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital. Methods The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients’ intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for CYP2C9*2 rs179985, CYP2C9*3 rs1057910, CYP2C8*3 rs11572080, CYP2C8*3 rs10509681, PTGS-1 rs10306135, PTGS-1 rs12353214, and PTGS-2 rs20417 using real-time PCR. Results In NSAIDs+ patients, PTGS1 rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95 % CI=1.30–22.27). In total sample, smoking (OR=3.12, 95 % CI=1.15–8.46), and alcohol intake (OR=4.09, 95 % CI=1.05–15.87) increased odds of gastrointestinal damage. In NSAIDs+ patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95 % CI=0.04–0.93) and two gastroprotectors (OR=0.13, 95 % CI=0.02–0.75) reduced the chance of upper gastrointestinal lesions. Conclusions Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries.

Funder

Russian Science Foundation

Publisher

Walter de Gruyter GmbH

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