CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes

SIMPLE SUMMARY: CYP2C19 is known as an enzyme primarily responsible for metabolizing various drugs, such as proton pump inhibitor, antiplatelet, anti-epileptic, and anticoagulant. CYP2C19 is known to be polymorphic and can result in the clinical efficacy of drugs. To examine the prevalence and the distribution of the CYP2C19 genetic polymorphisms in Indonesia, we performed polymerase chain reaction-restriction fragment length polymorphism to the genomic DNA of Indonesian participants. In addition, we also analyzed the distribution of CYP2C19 polymorphisms among ethnicities and clinical outcomes. We found that the prevalence of intermediate metabolizers were the highest in Indonesia, followed by rapid metabolizers and poor metabolizers, respectively. The distribution of metabolizer groups were different between ethnic groups in Indonesia. Therefore, dosage adjustment should be considered when administering drugs-affected by CYP2C19 in Indonesia. The results presented in this study showed the distribution of CYP2C19 variant alleles at the population level in Indonesia and might be used as a consideration for providing personalized treatment in clinical practice. ABSTRACT: CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.