CYP2C19 Phenotype and Risk of Proton Pump Inhibitor-Associated Infections.

Area of Science:

• Pharmacogenomics
• Pediatric Gastroenterology
• Infectious Diseases

Background:

• Proton pump inhibitors (PPIs) are widely used in children for gastrointestinal issues.
• Concerns exist regarding increased infection risk associated with PPI use in pediatric populations.
• CYP2C19 enzyme activity influences PPI metabolism; genetic variants affecting its function are of interest.

Purpose of the Study:

• To investigate the association between CYP2C19 metabolizer phenotypes and infection rates in children exposed to PPIs.
• To determine if genetic variations in CYP2C19 impact the risk of infections in pediatric PPI users.

Main Methods:

• Retrospective cohort study of 670 children (0-36 months) exposed to PPIs.
• Infection events (respiratory, gastrointestinal) identified via ICD codes within one year of PPI exposure.
• CYP2C19 genetic variants (*2, *3, *4, *8, *9, *17) genotyped to classify metabolizer phenotypes (poor, intermediate, normal, rapid, ultrarapid).

Main Results:

• Children with normal CYP2C19 metabolizer function (NMs) had a higher infection rate compared to rapid/ultrarapid metabolizers (RM/UMs) (2 vs 1 infection/person/year, P=.03).
• No significant difference in infection rates was observed between poor/intermediate metabolizers and NMs.
• In multivariable analysis, CYP2C19 metabolizer status remained a significant factor for infection risk (OR 0.70 for RM/UMs vs NMs).

Conclusions:

• PPI therapy is linked to elevated infection rates in pediatric patients with normal CYP2C19 function.
• Individuals with increased CYP2C19 function (RM/UMs) experienced fewer PPI-associated infections.
• CYP2C19 genotype may be relevant for guiding PPI therapeutic decisions in children.