AUTHOR=Forgerini Marcela , Urbano Gustavo , De Nadai Tales Rubens , Batah Sabrina Setembre , Fabro Alexandre Todorovic , De Carvalho Mastroianni Patrícia 

TITLE=The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study

JOURNAL=Journal of Pharmacy & Pharmaceutical Sciences

VOLUME=26

YEAR=2023

URL=https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences/articles/10.3389/jpps.2023.11136

DOI=10.3389/jpps.2023.11136

ISSN=1482-1826

ABSTRACT=<p><bold>Purpose:</bold> To investigate whether interindividual variability in the <italic>CYP2C9</italic> (*2 and *3 alleles) and <italic>VKORC1</italic> (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA).</p><p><bold>Methods:</bold> A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD &gt;0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI).</p><p><bold>Results:</bold> For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41–174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70–556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the <italic>CYP2C9</italic> and <italic>VKORC1</italic> genes. No synergism was identified.</p><p><bold>Conclusion:</bold> Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user.</p>