Genetic Polymorphism of CYP2C19 in Pakistani Population

Area of Science:

• Pharmacogenomics
• Human Genetics
• Drug Metabolism

Background:

• CYP2C19 genetic variations influence drug metabolism and response.
• Pakistan's diverse ethnic groups necessitate population-specific pharmacogenetic studies.
• Understanding CYP2C19 allele frequencies is crucial for personalized medicine and preventing adverse drug reactions.

Purpose of the Study:

• To determine the prevalence of CYP2C19*2 and CYP2C19*17 alleles across nine major ethnic groups in Pakistan.
• To investigate the distribution of CYP2C19 genetic polymorphisms within these diverse populations.
• To provide data for optimizing drug therapy and minimizing adverse drug reactions in the Pakistani population.

Main Methods:

• Genotyping of CYP2C19*2 and CYP2C19*17 alleles using allele-specific amplification polymerase chain reaction (ASA-PCR).
• Analysis of DNA samples from 1028 healthy volunteers representing nine distinct ethnic groups.
• Phenotype prediction (EM, PM, IM, UM) based on identified CYP2C19 genotypes.

Main Results:

• The overall frequency of predicted poor metabolizer (PM) alleles was 29.0%, and ultra-rapid metabolizer (UM) alleles was 23.70%.
• Saraiki and Brahui ethnic groups exhibited the highest percentages of PM alleles (40% and 36%, respectively).
• Parsi and Hazara ethnic groups showed the highest percentages of UM alleles (37% and 30%, respectively).

Conclusions:

• Significant variations in CYP2C19 allele frequencies exist among Pakistani ethnic groups.
• The high prevalence of PM alleles underscores the need for pre-treatment genetic testing.
• Personalized medicine approaches, including genotype-guided drug selection and dosage, are recommended to improve therapeutic outcomes and patient safety in Pakistan.