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Genetic and epigenetic polymorphisms of eNOS and CYP2D6 in mainland Chinese Tibetan, Mongolian, Uygur, and Han populations

The Pharmacogenomics Journal volume 20, pages 114–125 (2020)Cite this article

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Abstract

Cytochrome P450 2D6 (CYP2D6) and endothelial nitric oxide synthase (eNOS) are important in the cardiovascular disease susceptibility and drug response. The methylation of cytosine in the promoter of genes could influence expression. The interindividual differences of drug response could only be explained partly by the polymorphisms of drug disposition genes. This study was aimed to investigate the genetic and epigenetic polymorphisms of CYP2D6 and eNOS in Chinese Tibetan, Mongolian, Uygur, and Han volunteers. Blood samples were collected from 842 unrelated Chinese healthy subjects (323 Tibetan, 134 Mongolian, 162 Uygur, and 223 Han) for genotyping and part of the DNA samples were subjected to cytosine methylation analysis. Significant genetic and epigenetic interethnic polymorphisms of eNOS and CYP2D6 were found in the four Chinese groups. The 4b-G-T wild-type haplotype of eNOS was the most common in Chinese Tibetan (87.1%), Mongolian (79.9%), Uygur (76.4%), and Han (79.5%), respectively. eNOS T-786C creates a new CpG site and a significantly higher methylation level was found in −786CC than that in −786TC in Chinese Han (P = 0.0485) and total Chinese (P = 0.0104). CYP2D6 A-678 (rs28633410) makes the symmetrical CpG site changed to be an asymmetrical CpA site, and the methylation level of cytosine in the CpG context of G-678A was significantly higher than that in the CpA. The results of the present study could be useful for understanding the interindividual disparity of cardiovascular disease susceptibility and drug response among different Chinese ethnic groups and would provide more evidences for the precise medication of Chinese.

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Acknowledgements

The study was supported by the National Natural Science Foundation of China (Grants No. 30973585 and No. 91029747), and the Beijing University Center for Human Disease Genomics (Grant No. 2000A-1).

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Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Guangzhao Qi

  2. Department of Pharmacology, Basic Medical School, Peking University, Beijing, China

    Guangzhao Qi, Shengju Yin, Guoliang Zhang & Xin Wang

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Correspondence to Guangzhao Qi.

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Qi, G., Yin, S., Zhang, G. et al. Genetic and epigenetic polymorphisms of eNOS and CYP2D6 in mainland Chinese Tibetan, Mongolian, Uygur, and Han populations. Pharmacogenomics J 20, 114–125 (2020). https://doi.org/10.1038/s41397-019-0104-2

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