Elsevier

Biological Psychiatry

Volume 62, Issue 6, 15 September 2007, Pages 635-641
Biological Psychiatry

Original Article
CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial

https://doi.org/10.1016/j.biopsych.2006.10.005Get rights and content

Background

CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome.

Methods

Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants.

Results

Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05–8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98–9.06, p = .05).

Conclusions

These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.

Section snippets

Participants

Participants were enrolled from April 1999 to October 2001 at Georgetown University (Washington, DC) and State University of New York (SUNY) Buffalo (New York). Recruitment, demographics, and the protocol have been reported in detail elsewhere (Lerman et al 2002, Lerman et al 2006). A total of 555 participants enrolled in the pharmacogenetic trial, of whom 423 were successfully genotyped; the rest had insufficient DNA remaining for this analysis. Of the 423 for whom CYP2B6 genotyping was

Results

In our sample, 423 participants were successfully genotyped, including 342 Caucasians. The CYP2B6*9 allele was not found. The Caucasian genotype frequencies were CYP2B6*1/*1 (52.3%), CYP2B6*1/*6 (36.3%), CYP2B6*6/*6 (6.7%), CYP2B6*1/*4 (4.1%), and CYP2B6*4/*6 (.6%). The Caucasian CYP2B6*6 and CYP2B6*4 allele frequencies were 25.2% and 2.3%, respectively (n = 342 total); both alleles were in Hardy-Weinberg equilibrium (p = .96 and p = .53, respectively). Smokers with a CYP2B6*1/*4 genotype,

Discussion

This study illustrates the importance of investigating genetic variation in drug-metabolizing enzymes to predict smoking cessation and therapeutic response to bupropion. Without investigating CYP2B6 genetics, the overall effect on abstinence of bupropion is modest. However, when CYP2B6 genotype is incorporated, bupropion is significantly more efficacious than placebo for ∼45% of the population (those in the CYP2B6*6 group) but not in the remaining ∼55% (those in the CYP2B6*1 group). At EOT, the

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