Frequency of CYP2C19 Genotypes among Palestinian Population and Detection of its effect on cure rates of GERD by Omeprazole رسالة ماجستير

Abstract

Background and Objectives:. Gastroesophageal Reflux Disease (GERD)is a chronic disease caused by the flow of stomach contents in opposite direction upward the esophagus. GERD affects 35% of the adult population in the western world12 . It is considered a major indication for Proton Pump inhibitors (PPI’s) treatment. PPI’s including the major drug Omeprazole are first line drugs used as acid inhibitors for many diseases including GERD. However, several patients don’t respond or respond poorly to the usual dose of one of the common PPI’s. Accordingly, factors that affect treatment success by these drugs should be determined to ensure maximum benefit to patients. For GERD patients who take Omeprazole as treatment, clinical response varies among them according to CYP2C19 polymorphisms. The aim of our study was to assess the frequency of CYP2C19 gene haplotypes among Palestinian GERD patients treated with Omeprazole including CYP2C19/2*, CYP2C19/3*, and CYP2C19/17*. Methods: The study included 73 Palestinian patients with GERD, 24 were non-responders to Omeprazole and 36 were responders to Omeprazole. DNA samples were obtained and genotyped for CYP2C19/2*, CYP2C19/17*, and CYP2C19/3*by ARMS-PCR. SNPStat software were used to analyze the generated data. Results: Our data revealed that there was a statically significant difference between responders and non- responders who have G/A and G/G genotypes ( P= 0.0001) in CYP2C19/2* that has an association with the clinical response of Omeprazole in GERD patients. However, our data show no statistical significance between responders and non responders regardless CYP2C19/3* of A/A and G/A genotypes (P=0.72) and CYP2C19/17* of C/C and C/T genotypes (P= 0.2). Our data demonstrate the importance of CYP2C19 polymorphisms screening to assess the suitable dose of Omeprazole for VI patients to treat GERD. This helps in minimizing the adverse drug reactions and maximize the effect of Omeprazole as much as possible in treating GERD. Conclusion: The data revealed significant correlation between CYP2C19/2* genotypes and clinical response of GERD patients to Omeprazole with no significant correlation with other SNP’s including CYP2C19/17* and CYP2C19/3*. Further investigations on a larger sample for wider representation of the population and including additional CYP2C19 SNP’s that may affect the expression of the gene will provide better correlation between clinical response and the indicated gene variants