Genetic variants, haplotype determination, and function of novel alleles of CYP2B6 in a Han Chinese population

The study aimed to investigate the genetic variants of the CYP2B6 gene in a Han Chinese population and assess the impact of these variants on enzyme activity, with a focus on precision medicine applications. The research sequenced the CYP2B6 gene in 1483 individuals from Zhejiang Province using Sanger sequencing and evaluated the catalytic activity of novel nonsynonymous variants using in vitro methods. Additionally, haplotype determination was performed using Oxford Nanopore sequencing to provide more detailed insight into the genetic structure of these variants.

Oxford Nanopore sequencing, specifically the GridION platform, was used to determine the haplotypes of novel variants, which could not be fully resolved by traditional sequencing methods. This allowed the researchers to assign 11 novel star alleles (CYP2B6 *39–49) based on their haplotypes.

The major findings of the study revealed 7 previously reported CYP2B6 alleles and 18 novel variants, including 11 nonsynonymous ones that exhibited significantly lower catalytic activity compared to the wild-type CYP2B6 *1 allele. The novel alleles showed a reduced ability to metabolize bupropion and efavirenz, which are substrates for CYP2B6. The researchers concluded that these novel alleles could have important implications for pharmacogenetics, influencing drug dosing recommendations to ensure effective and safe treatments for patients carrying these variants.