Research on genetic variant characteristics in ADME genes based on whole-exome sequencing in the Han Chinese population

We integrated 604 ADME genes and 972 drugs. There were 33,925 single nucleotide polymorphisms (SNPs) and 484 insertion-deletions (InDels) in 5,357 Han Chinese WES samples; 88.9 % were rare. Of the SNPs, 60.9 % are new functional mutations in enzyme and transporter genes; InDels also affected these genes. We discovered Chinese-specific variants in key ADME genes and ethnic-specific metabolic phenotypes that could affect drug use. Finally, we screened 3,657 potentially harmful mutations; 45.6 % are novel. Western blotting and enzyme activity assays confirmed several harmful mutations significantly reduced CYP2C19 gene expression and function (P < 0.01).