Ethnic Differences in Genetic Polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1

Abstract

Metabolic capacities for debrisoquin, sparteine, mephenytoin, nifedipine, and midazolam, which are substrates of polymorphic CYP2D6, CYP2C19, and CYP3A, have been reported to exhibit, in many cases, remarkable interindividual and ethnic differences. These ethnic differences are partly associated with genetic differences. In the case of the drug transporter ABCB1/MDR1, interindividual differences in its transporter activities toward various clinical drugs are also attributed to several ABCB1/MDR1 genetic polymorphisms. In this review, the existence and frequency of various low-activity alleles of drug metabolizing enzymes as well as populational drug metabolic capacities are compared among several different races or ethnicities. Distribution of nonsynonymous ABCB1/MDR1 SNPs and haplotype frequency in various races are summarized, with the association of nonsynonymous SNPs with large functional alterations as a rare event.

In Vitro-In Vivo Extrapolation Scaling Factors for Intestinal P-Glycoprotein and Breast Cancer Resistance Protein: Part I: A Cross-Laboratory Comparison of Transporter-Protein Abundances and Relative Expression Factors in Human Intestine and Caco-2 Cells

“…is not detected in other populations, including Caucasians (n = 100), Asian Americans (n = 30), Mexican Americans (n = 10), Pacific Islanders (n = 7), and Japanese (n = 145) (Kroetz et al, 2003;Ozawa et al, 2004). The standard peptide selected for P-gp quantification by BPh was flagged as having the potential for a trypsin missed cleavage event by ConSEQuence (Lawless and Hubbard, 2012).…”

Genetic Determinants of CYP2C19 Gene *2 and *3 Loss of Function Alleles and Response to Anti Platelet Therapy (Clopidogrel) and Cardiovascular Events. (A Study in Kashmir, North India)

“…The patients were included on criteria like ACS with or without undergoing PCI, ST Elevation Myocardial Infarction (STEMI), Non ST Elevation Myocardial Infarction (NSTEMI) and those with Unstable Angina (USA). The patients who include history of bleeding diathesis, stroke less than 3 months platelet count <70000/mm 3 , hematocrit <30% were excluded from the study. Written informed consent was obtained from all the study participants.…”

“…The CYP2C19*3 is mainly found in Asians (5-9% in Asians, less than 0.5% in Caucasians). The allelic frequency of CYP2C19*17 has been shown to be 16% in Africans, 3-6% in Asians and 16-21% in Caucasians [3].…”

Genetic polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in Vietnamese-Koreans

“…Many countries such as United States, Unites Kingdom, and some European countries have been experienced the multi-ethnicities and multi-cultures in their countries and have already launched pharmacogenetic research program for their nationals. [3][4][5][6] Individual differences in capacity to metabolize drugs can be TCP Transl Clin Pharmacol affected by genetic polymorphisms in drug metabolizing enzymes such as phase I and phase II enzymes. Cytochrome P450 (CYP) is accounted as a major phase I enzyme consisting of about 75 percent of the phase I enzyme.…”