Prevalence of the CYP2C19*2 (681 G>A), *3 (636 G>A) and *17 (‑806 C>T) alleles among an Iranian population of different ethnicities

Abstract

Polymorphisms in the cytochrome P (CYP) 450 family may cause adverse drug responses in individuals. Cytochrome P450 2C19 (CYP2C19) is a member of the CYP family, where the presence of the 681 G>A, 636 G>A and 806 C>T polymorphisms result in the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. In the current study, the frequency of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles in an Iranian population cohort of different ethnicities were examined and then compared with previously published frequencies within other populations. Allelic and genotypic frequencies of the CYP2C19 alleles (*2, *3 and *17) were detected using polymerase chain reaction (PCR)‑restriction fragment length polymorphism analysis, PCR‑single‑strand conformation polymorphism analysis and DNA sequencing from blood samples of 1,229 unrelated healthy individuals from different ethnicities within the Iranian population. The CYP2C19 allele frequencies among the Iranian population were 21.4, 1.7, and 27.1% for the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. The frequency of the homozygous A/A variant of the CYP2C19*2 allele was significantly high and low in the Lur (P<0.001) and Caspian (P<0.001) ethnicities, respectively. However, the frequency of the homozygous A/A variant of the CYP2C19*3 allele was not detected in the Iranian cohort in the current study. The frequency of the heterozygous G/A variant of the CYP2C19*3 allele had the significantly highest and lowest frequency in the Fars (P<0.001) and Lur (P<0.001) groups, respectively. The allele frequency of the homozygous T/T variant of the CYP2C19*17 allele was significantly high in the Caspian (P<0.001) and low in the Kurd (P<0.05) groups. The frequency of the CYP2C19 alleles involved in drug metabolism, may improve the clinical understanding of the ethnic differences in drug responses, resulting in the advancement of the personalized medicine among the different ethnicities within the Iranian population.

Keywords: CYP2C19*3 allele; Kurd; Lur; Caspian; Iranian populations; Fars; CYP2C19; Turk.

Figure 1.

DNA sequencing chromatograms of CYP2C19*2, *3 and *17. (A) Homozygous mutant CYP2C19*2 (A/A), heterozygous mutant CYP2C19*2 (G/A) and wild-type CYP2C19 (G/G). (B) Wild-type CYP2C19 (G/G), and heterozygous mutant CYP2C19*3 (G/A). (C) Wild-type CYP2C19 (C/C), heterozygous mutant CYP2C19*17 (C/T) and homozygous mutant CYP2C19*17 (T/T). CYP2C19, cytochrome P450 2C19.

Figure 2.

PCR-RFLP analysis. (A) The PCR products were disgusted with SmaI, producing 50-bp and 118-bp fragments for wild type allele, and one fragment of 168-bp for the allele carrying the CYP2C19*2681 G>A substitution. (B) The PCR product is disgusted with BamHI, producing 26 and 93-bp fragments for the wild type allele, and one fragment of 119-bp for the allele carrying the CYP2C19*3636 G>A substitution. (C) The PCR product was disgusted with LweI, producing 114, 184, 34 and 139-bp fragments for the wild type allele, and three fragments in size 218, 139 and 114-bp for the allele carrying the CYP2C19*17-806 C>T substitution. DNA fragments with size of >50 bp were not visible. PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; CYP2C19, cytochrome P450 2C19.

Figure 3.

Polymerase chain reaction-single-strand conformation polymorphism analysis of the (A) CYP2C19*2 (B) CYP2C19*3 and (C) CYP2C19*17). Two, three and four bands in each lane represent the homozygous mutant, homozygous wild-type, and heterozygous alleles of the CYP2C19*2 and *3, and *17. CYP2C19, cytochrome P450 2C19.

Figure 4.

The CYP2C19*2, *3 and *17 alleles distribution among different Iranian ethnicities including Fars, Turk, Caspian, Lure and Kurd populations. The highest frequency of the CYP2C19*2 allele was found in Lure individuals (35%) and the lowest frequency was found in Caspian individuals (9.6%). The highest frequency of the CYP2C19*3 allele was found in Fars individuals (2.92%) and the lowest frequency was found in Lure individuals (0.68%). The highest frequency of the CYP2C19*17 allele was found in Lure individuals (46.15%) and the lowest frequency was found in Caspian individuals (17.18%). The red, blue, green, yellow and pink colors indicate the Fars, Turk, Caspian, Lure and Kurd regions. CYP2C19, cytochrome P450 2C19.

Figure 5.

Frequency of the CYP2C19*3 allele in different countries around the world. The highest incidence of the CYP2C19*3 allele has been reported in Indonesians (37%). The second highest CYP2C19*3 frequency has been reported in the Iruna population from New Guinea (34%). It seems that the allelic frequency of CYP2C19*3 increases from the west to the east of Asia. CYP2C19, cytochrome P450 2C19.