Cytochrome P450 2C9 Gene Polymorphism and Losartan Response in Essential Hypertensive Patients. A Pharmacogenetic Association Study in Iraq

Abstract Background: In today’s clinical practice, drug research, and drug regulation, one of the most significant challenges is interindividual diversity in therapeutic efficacy and safety. Pharmacogenetics is now in its early phase of development in Iraq. Limited pharmacogenetic data exist about the prevalence and impact of CYP2C9 gene polymorphism within the Iraqi population. Objectives: This study examines the potential impact of CYP2C9 gene polymorphisms (namely, rs1799853 and rs1057910) on the therapeutic response to losartan in a cohort of Iraqi patients diagnosed with essential hypertension. Material and Methods: This prospective interventional clinical study was conducted on a sample of hypertension patients from Babylon governorate in Iraq. For all selected patients, blood pressure was measured. Then they received 100 mg of losartan once daily, after 4 weeks of losartan therapy, blood pressure was reassessed and compared with its initial values, and the changes were recorded. Blood samples were obtained from all patients for genetic analysis, employing established methodologies. The genotyping of CYP2C9 rs1799853 and rs1057910 variant alleles was conducted using the Sanger sequencing method. Subsequently, the treatment responses of patients with polymorphic genotypes were compared to those of patients bearing the wild-type of genotype. Results: According to the findings of the present study, 28% of patients showed a positive response to losartan based on the predetermined criteria (a decrease in systolic blood pressure of at least 15% and diastolic blood pressure of at least 10%). No statistically significant differences P value < 0.05) were seen in the distribution of genotypes of both single nucleotide polymorphisms between the responder and nonresponder groups. Furthermore, a comparative study was conducted to examine the wild-type and heterozygous mutant genotype groups for both single nucleotide polymorphisms in terms of changes in systolic or diastolic blood pressure reduction. The results revealed that there was no statistically significant variation found between these two groups. Conclusion: The CYP2C9 gene polymorphism has no impact on the antihypertensive efficacy of losartan.