哮喘联盟

摘要
   前言：在近期的一项有关安非他酮和集中认知行为情感治疗的随机、双盲、安慰剂-对照临床试验中，对331名个体进行了纵向分析，结果显示DRD4外显子III 可变数目的串联重复序列（VNTR）变异能与安非他酮相互作用，影响未来戒烟。
   方法：我们采用单变量、多变量和纵向logistic回归，评价了基因、治疗、时间和交互作用对治疗结束、6个月和12个月时的点戒断和持续戒断的作用。416名欧洲裔受试者入选双盲、药物遗传学有效性试验，其中将受试者分为活性或安慰剂安非他酮组。参与者接受10周的药物治疗和7次的行为治疗，目标戒断日期为开始两项治疗后的2周。采用长期等位基因显性对VNTR的基因型进行编码，结果形成4个分析类别。协变量包括人口统计学指标、依赖性指标、抑郁症状和遗传血统。我们同时进行基因型分层的二级分析。
   结果：纵向分析两个戒断转归显示时间存在显著影响，治疗对VNTR长等位基因基因型个体的两个戒断转归存在显著影响，某些分析中协变量也存在显著影响。VNTR长等位基因基因型个体，活性 vs 安慰剂效应大于无VNTR长等位基因基因型个体，但无统计学差异。
   结论：治疗交互作用对VNTR的影响，本研究与前期研究存在差异，可能与样本量较小有关。对多个随机临床试验分析将有助于鉴别介导治疗反应的因素，并对其进行验证。

                                                                 (林江涛 审校)
                            Nicotine Tob Res. 2012 Dec 3. [Epub ahead of print]
 

The DRD4 Exon III VNTR, Bupropion, and Associations With Prospective Abstinence.

Bergen AW, Javitz HS, Su L, He Y, Conti DV, Benowitz NL, Tyndale RF, Lerman C, Swan GE.

Source
Center for Health Sciences, SRI International, Menlo Park, CA.

Abstract

NTRODUCTION: DRD4 Exon III Variable Number of Tandem Repeat (VNTR) variation was found to interact with bupropion to influence prospective smoking abstinence, in a recently published longitudinal analyses of N = 331 individuals from a randomized double-blind placebo-controlled trial of bupropion and intensive cognitive-behavioral mood management therapy.
METHODS: We used univariate, multivariate, and longitudinal logistic regression to evaluate gene, treatment, time, and interaction effects on point prevalence and continuous abstinence at end of treatment, 6 months, and 12 months, respectively, in N = 416 European ancestry participants in a double-blind pharmacogenetic efficacy trial randomizing participants to active or placebo bupropion. Participants received 10 weeks of pharmacotherapy and 7 sessions of behavioral therapy, with a target quit date 2 weeks after initiating both therapies. VNTR genotypes were coded with the long allele dominant resulting in 4 analysis categories. Covariates included demographics, dependence measures, depressive symptoms, and genetic ancestry. We also performed genotype-stratified secondary analyses.
RESULTS: We observed significant effects of time in longitudinal analyses of both abstinence outcomes, of treatment in individuals with VNTR long allele genotypes for both abstinence outcomes, and of covariates in some analyses. We observed non-significantly larger differences in active versus placebo effect sizes in individuals with VNTR long allele genotypes than in individuals without the VNTR long allele, in the directions previously reported.
CONCLUSIONS: VNTR by treatment interaction differences between these and previous analyses may be attributable to insufficient size of the replication sample. Analyses of multiple randomized clinical trials will enable identification and validation of factors mediating treatment response.

Nicotine Tob Res. 2012 Dec 3. [Epub ahead of print]