TY - JOUR

T1 - Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion-aided smoking cessation in African Americans?

T2 - A moderated mediation analysis

AU - Chenoweth, Meghan J

AU - Peng, Annie R

AU - Zhu, Andy Z X

AU - Cox, Lisa Sanderson

AU - Nollen, Nikki L

AU - Ahluwalia, Jasjit S

AU - Benowitz, Neal L

AU - Knight, Jo

AU - Swardfager, Walter

AU - Tyndale, Rachel F

N1 - This is the peer reviewed version of the following article: Chenoweth, MJ, Peng, AR, Zhu, AZX, Cox, LS, Nollen, NL, Ahluwalia, JS, et al. Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion-aided smoking cessation in African Americans? A moderated mediation analysis. Addiction. 2022; 117: 1715– 1724. https://doi.org/10.1111/add.15742 which has been published in final form at: https://onlinelibrary.wiley.com/doi/10.1111/add.15742 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

PY - 2022/6/30

Y1 - 2022/6/30

N2 - BACKGROUND AND AIMS: CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion-aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion-aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex.DESIGN AND SETTING: Secondary analysis of a smoking cessation clinical trial (NCT00666978).PARTICIPANTS/CASES: African American light smokers (≤ 10 cigarettes/day).INTERVENTIONS: Participants were treated with bupropion for 7 weeks.MEASUREMENTS: Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased-function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow-up (26 weeks).FINDINGS: Normal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample.CONCLUSIONS: In African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.

AB - BACKGROUND AND AIMS: CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion-aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion-aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex.DESIGN AND SETTING: Secondary analysis of a smoking cessation clinical trial (NCT00666978).PARTICIPANTS/CASES: African American light smokers (≤ 10 cigarettes/day).INTERVENTIONS: Participants were treated with bupropion for 7 weeks.MEASUREMENTS: Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased-function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow-up (26 weeks).FINDINGS: Normal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample.CONCLUSIONS: In African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.

KW - Buproprion

KW - CYP2B6

KW - Hydroxybuproprion

KW - Meditation analyses

KW - Pharmacogenetics

KW - Sex differences

KW - Smoking cessation

U2 - 10.1111/add.15742

DO - 10.1111/add.15742

M3 - Journal article

C2 - 34791718

VL - 117

SP - 1715

EP - 1724

JO - Addiction

JF - Addiction

SN - 0965-2140

IS - 6

ER -