CYP2B6 non-coding variation associated with smoking cessation is also associated with differences in allelic expression, splicing, and nicotine metabolism independent of common amino-acid changes

A. Joseph Bloom, Maribel Martinez, Li Shiun Chen, Laura J. Bierut, Sharon E. Murphy, Alison Goate

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The Cytochrome P450 2B6 (CYP2B6) enzyme makes a small contribution to hepatic nicotine metabolism relative to CYP2A6, but CYP2B6 is the primary enzyme responsible for metabolism of the smoking cessation drug bupropion. Using CYP2A6 genotype as a covariate, we find that a non-coding polymorphism in CYP2B6 previously associated with smoking cessation (rs8109525) is also significantly associated with nicotine metabolism. The association is independent of the well-studied non-synonymous variants rs3211371, rs3745274, and rs2279343 (CYP2B6*5 and*6). Expression studies demonstrate that rs8109525 is also associated with differences in CYP2B6 mRNA expression in liver biopsy samples. Splicing assays demonstrate that specific splice forms of CYP2B6 are associated with haplotypes defined by variants including rs3745274 and rs8109525. These results indicate differences in mRNA expression and splicing as potential molecular mechanisms by which non-coding variation in CYP2B6 may affect enzymatic activity leading to differences in metabolism and smoking cessation.

Original languageEnglish
Article numbere79700
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 15 2013

Fingerprint Dive into the research topics of 'CYP2B6 non-coding variation associated with smoking cessation is also associated with differences in allelic expression, splicing, and nicotine metabolism independent of common amino-acid changes'. Together they form a unique fingerprint.

  • Cite this