Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome P450 2C19 gene in six major ethnicities of Pakistan

Abstract

Interindividual differences in cytochrome P450 (CYP) 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for CYP2C19*2 and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for CYP2C19*2 and 8.14% for CYP2C19*3. For CYP2C19*2, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for CYP2C19*3, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.

Effects of genetic polymorphism of drug-metabolizing enzymes on the plasma concentrations of antiepileptic drugs in Chinese population

“…Ahmed et al . [ 14 ] have investigated the genetic polymorphisms of CYP2C19 in the healthy individuals of six distinct ethnic populations of Pakistan. The results show that the minor allele is present at a frequency of 15.06% and 8.14% for CYP2C19*2 and CYP2C19*3 , respectively, suggesting that a significant portion of the Pakistani population and its certain ethnic groups contain high frequencies of polymorphisms with reduced functions.…”

Variations in the Frequencies of Polymorphisms in the CYP450s Genes in Eight Major Ethnicities of Iran: A Review of the Human Data

“…Primarily, an effort has been made to genetically assess the specific populations, such as the people of a country, and compare them to other countries [6][7][8]. Following that, the ethnicities of various countries have been studied and compared [9][10][11]. Such assessments/studies greatly help access the required information and individualized therapies.…”