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Direct sequencing and comprehensive screening of genetic polymorphisms on CYP2 family genes (CYP2A6, CYP2B6, CYP2C8, and CYP2E1) in five ethnic populations

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Abstract

Recently, CYP2A6, CYP2B6, CYP2C8, and CYP2E1 have been reported to play a role in the metabolic effect of pharmacological and carcinogenic compounds. Moreover, genetic variations of drug metabolism genes have been implicated in the interindividual variation in drug disposition and pharmacological response. To define the distribution of single nucleotide polymorphisms (SNPs) in these four CYP2 family genes and to discover novel SNPs across ethnic groups, 288 DNAs composed of 48 African-Americans, 48 European-Americans, 48 Japanese, 48 Han Chinese, and 96 Koreans were resequenced. A total of 143 SNPs, 26 in CYP2A6, 45 in CYP2B6, 29 in CYP2C8, and 43 in CYP2E1, were identified, including 13 novel variants. Notably, two SNPs in the regulatory regions, a promoter SNP rs2054675 and a nonsynonymous rs3745274 (p.172Q>H) in CYP2B6, showed significantly different minor allele frequencies (MAFs) among ethnic groups (minimum P = 4.30 × 10−12). In addition, rs2031920 in the promoter region of CYP2E1 showed a wide range of MAF between different ethnic groups, and even among other various ethnic groups based on public reports. Among 13 newly discovered SNPs in this study, 5 SNPs were estimated to have potential functions in further in silico analyses. Some differences in genetic variations and haplotypes of CYP2A6, CYP2B6, CYP2C8, and CYP2E1 were observed among populations. Our findings could be useful in further researches, such as genetic associations with drug responses.

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Acknowledgments

This research was supported by a grant (11182MFDS658) from Ministry of Food and Drug Safety in 2011.

Conflict of interest

The authors declare no conflict of interest with this work.

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Authors and Affiliations

  1. Department of Life Science, Sogang University, Seoul, Republic of Korea

    Jeong-Hyun Kim, Lyoung Hyo Kim & Hyoung Doo Shin

  2. Institute for Basic Science, Sogang University, Seoul, Republic of Korea

    Jeong-Hyun Kim & Hyoung Doo Shin

  3. Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Republic of Korea

    Hyun Sub Cheong, Byung Lae Park, Lyoung Hyo Kim & Hyoung Doo Shin

  4. Department of Toxicological Evaluation and Research, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Osong-eup, Cheongwon-gun, Chungcheongbuk-do, Republic of Korea

    Hee Jung Shin, Han Sung Na & Myeon Woo Chung

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  1. Jeong-Hyun Kim
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Correspondence to Hyoung Doo Shin.

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Jeong-Hyun Kim and Hyun Sub Cheong have contributed equally to this work.

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Kim, JH., Cheong, H.S., Park, B.L. et al. Direct sequencing and comprehensive screening of genetic polymorphisms on CYP2 family genes (CYP2A6, CYP2B6, CYP2C8, and CYP2E1) in five ethnic populations. Arch. Pharm. Res. 38, 115–128 (2015). https://doi.org/10.1007/s12272-014-0348-y

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