Munafò M R, Elliot K M, Murphy M F G, Walton R T, Johnstone E C
Department of Experimental Psychology, University of Bristol, Bristol, UK.
Pharmacogenomics J. 2007 Oct;7(5):353-61. doi: 10.1038/sj.tpj.6500432. Epub 2007 Jan 16.
We investigated the association of the OPRM1 genotype with long-term smoking cessation and change in body mass index (BMI) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy (NRT) patch or placebo in a randomized controlled trial, and were followed-up over an 8-year period following their initial cessation attempt. We also investigated possible sex differences in these relationships, given evidence for sex differences in smoking cessation and central opioid mechanisms, as well as some evidence for sex differences in response to NRT. Our results indicate that OPRM1 genotype may moderate the effect of transdermal nicotine patch compared to placebo during active treatment, with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch. Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt, with ex-smokers demonstrating an increase in BMI, and this increase being greater in female subjects than in male subjects. We did not observe any association of OPRM1 genotype with change in BMI, although there was a trend for genotype to influence the observed sex difference in change in BMI over time. Future studies should attempt to replicate these findings, and investigate the relationship between both short- and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes. Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption.
在一项随机对照试验中，我们对尝试使用尼古丁替代疗法（NRT）贴片或安慰剂戒烟的吸烟者进行了研究，调查了OPRM1基因型与长期戒烟以及戒烟尝试后体重指数（BMI）变化之间的关联，并在他们首次戒烟尝试后的8年时间里对其进行了随访。鉴于戒烟和中枢阿片类机制存在性别差异，以及对NRT的反应也有一些性别差异的证据，我们还研究了这些关系中可能存在的性别差异。我们的结果表明，在积极治疗期间，与安慰剂相比，OPRM1基因型可能会调节经皮尼古丁贴片的效果，仅OPRM1 AA基因型组显示出积极的NRT治疗有益，而携带一个或多个G等位基因拷贝的人则显示积极的NRT与安慰剂贴片相比没有益处。我们的结果还表明，戒烟尝试后8年随访时BMI变化存在性别差异，戒烟者的BMI有所增加，且女性受试者的增加幅度大于男性受试者。我们没有观察到OPRM1基因型与BMI变化之间存在任何关联，尽管基因型有随着时间影响观察到的BMI变化中性别差异的趋势。未来的研究应尝试重复这些发现，并调查短期和长期体重增加与戒烟之间的关系，以及可能构成这些过程基础的机制。未来的研究还应调查OPRM1基因型和戒烟对其他诸如饮酒等食欲和奖励行为的作用。
