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CYP2D6 allele frequencies in Korean population, comparison with East Asian, Caucasian and African populations, and the comparison of metabolic activity of CYP2D6 genotypes

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Abstract

Cytochrome P450 (CYP) 2D6 is present in less than about 2% of all CYP enzymes in the liver, but it is involved in the metabolism of about 25% of currently used drugs. CYP2D6 is the most polymorphic among the CYP enzymes. We determined alleles and genotypes of CYP2D6 in 3417 Koreans, compared the frequencies of CYP2D6 alleles with other populations, and observed the differences in pharmacokinetics of metoprolol, a prototype CYP2D6 substrate, depending on CYP2D6 genotype. A total of 3417 unrelated healthy subjects were recruited for the genotyping of CYP2D6 gene. Among them, 42 subjects with different CYP2D6 genotypes were enrolled in the pharmacokinetic study of metoprolol. The functional allele *1 and *2 were present in frequencies of 34.6 and 11.8%, respectively. In decreased functional alleles, *10 was the most frequent with 46.2% and *41 allele was present in 1.4%. The nonfunctional alleles *5 and *14 were present at 4.5 and 0.5% frequency, respectively. The *X × N allele was present at a frequency of 1.0%. CYP2D6*1/*1, *1/*2 and *2/*2 genotypes with normal enzyme activity were present in 12.1%, 8.6% and 1.4% of the subjects, respectively. CYP2D6*5/*5, *5/*14, and *14/*14 genotypes classified as poor metabolizer were only present in 4, 2, and 1 subjects, respectively. Mutant genotypes with frequencies of more than 1% were CYP2D6*1/*10 (32.0%), *10/*10 (22.3%), *2/*10 (11.7%), *5/*10 (3.7%), *1/*5 (2.5%), and *10/*41 (1.2%). The relative clearance of metoprolol in CYP2D6*1/*10, *1/*5, *10/*10, *5/*10, and *5/*5 genotypes were 69%, 57%, 24%, 14% and 9% of CYP2D6*wt/*wt genotype, respectively. These results will be very useful in establishing a strategy for precision medicine related to the genetic polymorphism of CYP2D6.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2016R1A2B4007381).

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  1. Ji-Young Byeon, Young-Hoon Kim, Choong-Min Lee and Se-Hyung Kim have contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea

    Ji-Young Byeon, Young-Hoon Kim, Choong-Min Lee, Se-Hyung Kim, Won-Ki Chae, Eui-Hyun Jung, Choon-Gon Jang & Seok-Yong Lee

  2. College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Republic of Korea

    Chang-Ik Choi

  3. College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea

    Jung-Woo Bae

  4. College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea

    Yun Jeong Lee

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  1. Ji-Young Byeon
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Correspondence to Seok-Yong Lee, Jung-Woo Bae or Yun Jeong Lee.

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Byeon, JY., Kim, YH., Lee, CM. et al. CYP2D6 allele frequencies in Korean population, comparison with East Asian, Caucasian and African populations, and the comparison of metabolic activity of CYP2D6 genotypes. Arch. Pharm. Res. 41, 921–930 (2018). https://doi.org/10.1007/s12272-018-1075-6

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