Genetic variants, haplotype determination, and function of novel alleles of CYP2B6 in a Han Chinese population
Li-Qun Zhang,
Xin-Yue Li,
Lian-Guo Chen,
Zhe Chen,
Ren-Ai Xu,
Jian-Chang Qian,
Xiao-yang Zhou,
Da-Peng Dai,
Guo-Xin Hu,
Jian-Ping Cai
Affiliations
Li-Qun Zhang
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, China
Xin-Yue Li
Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
Lian-Guo Chen
The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China
Zhe Chen
Pharmacy department, Wenzhou people's hospital, 325000, Wenzhou, Zhejiang, China
Ren-Ai Xu
The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China
Jian-Chang Qian
Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
Xiao-yang Zhou
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, China
Da-Peng Dai
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, China
Guo-Xin Hu
Institute of Molecular Toxicology and Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
Jian-Ping Cai
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, China; Corresponding author.
Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The effects of nonsynonymous variants on recombinant protein catalytic activity were investigated in vitro with Sf12 system. The haplotype of novel nonsynonymous variants with other single nucleotide variants in the same allele was determined using Nanopore sequencing. Of 38 alleles listed on the Pharmacogene Variation Consortium, we detected 7 previously reported alleles and 18 novel variants, of which 11 nonsynonymous variants showed lower catalytic activity (0.00–0.60) on bupropion compared to CYP2B6*1. Further, these 11 novel star-alleles (CYP2B6*39–49) were assigned by the Pharmacogene Variation Consortium, which may be valuable for pharmacogenetic research and personalized medicine.
