No association between dopaminergic polymorphisms and response to treatment of binge-eating disorder

Gene. 2021 May 20:781:145538. doi: 10.1016/j.gene.2021.145538. Epub 2021 Feb 23.

Abstract

Background: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: Binge-eating; COMT; DAT-1; MAO-A; Obesity; Taq-1A.

MeSH terms

  • Adolescent
  • Adult
  • Binge-Eating Disorder / genetics*
  • Binge-Eating Disorder / metabolism
  • Catechol O-Methyltransferase / genetics
  • Cross-Sectional Studies
  • Dopamine / genetics*
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Monoamine Oxidase / genetics
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics
  • Receptors, Dopamine D2 / genetics
  • Young Adult

Substances

  • DRD2 protein, human
  • Receptors, Dopamine D2
  • Monoamine Oxidase
  • COMT protein, human
  • Catechol O-Methyltransferase
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases
  • Dopamine