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

被引:0
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作者
Guangzhao Qi
Shengju Yin
Guoliang Zhang
Xin Wang
机构
[1] The First Affiliated Hospital of Zhengzhou University,Department of Pharmacy
[2] Basic Medical School,Department of Pharmacology
[3] Peking University,undefined
来源
The Pharmacogenomics Journal | 2020年 / 20卷
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摘要
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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页码:114 / 125
页数:11
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