Heidinger Brandon A, Cameron Jameason D, Vaillancourt Regis, De Lisio Michael, Ngu Matthew, Tasca Giorgio A, Chyurlia Livia, Doucet Éric, Doucette Steve, Maria Obregón Rivas Ana, Goldfield Gary S
Healthy Active Living and Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, Canada.
Gene. 2021 May 20;781:145538. doi: 10.1016/j.gene.2021.145538. Epub 2021 Feb 23.
The genetics of binge-eating disorder (BED) is an emerging topic, with dopaminergic genes being implicated in its etiology due to the role that dopamine (DA) plays in food reward sensitivity and self-regulation of eating behavior. However, no study to date has examined if DA genes influence response to behavioral treatment of BED.
The primary objective of this study was to examine the ability of DA-associated polymorphisms to predict BED treatment response measured using binge frequency over 12 months. As secondary objectives, this study examined cross-sectional relationships between these polymorphisms and anthropometrics in women living with and without BED and obesity.
Women aged 18-64 years old were genotyped for the DA-related SNPs DRD2/ANKK1 Taq1A (rs1800497) and COMT (rs4680), as well as the DA-related uVNTRs DAT-1 (SLC6A3) and MAO-A. A multi-locus DA composite score was formed from these 4 polymorphisms using genotypes known to have a functional impact resulting in modified DA signaling. Binge frequency (Eating Disorder Examination - Interview) and body composition (Tanita BC-418) were assessed in a pre-post analysis to examine genetic predictors of treatment response in women living with obesity and BED. Secondary data analysis was conducted on a cross-sectional comparison of three groups of women enrolled in trial group treatment for BED: women living with obesity and BED (n = 72), obesity without BED (n = 27), and normal-weight without BED (n = 45).
There were no significant genotype × time interactions related to anthropometrics or binge frequency for any individual DA genotypes, or to the composite score reflecting DA availability. At baseline, there were no significant between-group differences in frequencies of DA-related alleles, nor were there associations between genotypes and anthropometrics.
Our study found no evidence to suggest that the DRD2/ANKK1 Taq1A, COMT, MAO-A, or DAT-1 polymorphisms are associated with response to behavioral intervention for BED as measured by changes in binge frequency. Future studies should examine a greater variety of dopaminergic polymorphisms, other candidate genes that target other neurotransmitter systems, as well as examine their impact on both behavioral and pharmacological-based treatment for BED.
暴饮暴食症（BED）的遗传学是一个新兴话题，由于多巴胺（DA）在食物奖励敏感性和饮食行为自我调节中所起的作用，多巴胺能基因被认为与其病因有关。然而，迄今为止尚无研究探讨DA基因是否会影响BED行为治疗的反应。
本研究的主要目的是检验与DA相关的多态性预测BED治疗反应的能力，该反应通过12个月内的暴饮暴食频率来衡量。作为次要目的，本研究考察了这些多态性与患有和未患有BED及肥胖症的女性的人体测量指标之间的横断面关系。
对18至64岁的女性进行与DA相关的单核苷酸多态性（SNP）DRD2/ANKK1 Taq1A（rs1800497）和儿茶酚-O-甲基转移酶（COMT，rs4680）以及与DA相关的可变数目串联重复序列（uVNTR）多巴胺转运体1（DAT-1，SLC6A3）和单胺氧化酶A（MAO-A）的基因分型。使用已知具有功能影响从而导致DA信号传导改变的基因型，由这4种多态性形成一个多位点DA综合评分。在前后分析中评估暴饮暴食频率（饮食失调检查访谈）和身体成分（Tanita BC-418），以检查肥胖和BED女性治疗反应的遗传预测因素。对参加BED试验组治疗的三组女性进行横断面比较的二次数据分析：患有肥胖和BED的女性（n = 72）、无BED的肥胖女性（n = 27）和无BED的正常体重女性（n = 45）。
对于任何单个DA基因型或反映DA可用性的综合评分，均未发现与人体测量指标或暴饮暴食频率相关的显著基因型×时间交互作用。在基线时，与DA相关的等位基因频率在组间无显著差异，基因型与人体测量指标之间也无关联。
我们的研究未发现证据表明DRD2/ANKK1 Taq1A、COMT、MAO-A或DAT-1多态性与通过暴饮暴食频率变化衡量的BED行为干预反应相关。未来的研究应考察更多种类的多巴胺能多态性、针对其他神经递质系统的其他候选基因，以及它们对BED行为治疗和药物治疗的影响。
