title: Contribution of BDNF and DRD2 genetic polymorphisms to continued opioid use in patients receiving methadone treatment for opioid use disorder: an observational study.
abstract: BACKGROUND
  The heritability of opioid use disorder has been widely investigated; however, the influence of specific genes on methadone treatment outcomes is not well understood. The association between response to methadone treatment and genes that are involved in substance use behaviors and reward mechanisms is poorly understood, despite evidence suggesting their contribution to opioid use disorder. The aim of this study was to investigate the effect of brain-derived neurotrophic factor (BDNF) and dopamine receptor D2 (DRD2) polymorphisms on continued opioid use among patients on methadone treatment for opioid use disorder.
  
  
  METHODS
  BDNF 196G>A (rs6265) and DRD2-241A>G (rs1799978) genetic variants were examined in patients with opioid use disorder who were recruited from methadone treatment clinics across Southern Ontario, Canada. We collected demographic information, substance use history, blood for genetic analysis, and urine to measure opioid use. We used regression analysis to examine the association between continued opioid use and genetic variants, adjusting for age, sex, ethnicity, methadone dose, duration in treatment, and number of urine screens.
  
  
  RESULTS
  Among 240 patients treated with methadone for opioid use disorder, 36.3 percent (n = 87) and 11.3 percent (n = 27) had at least one risk allele for rs6265 and rs1799978, respectively. These genetic variants were not significantly associated with continued opioid use while on methadone maintenance treatment [rs6265: odds ratio (OR) = 1.37, 95 % confidence interval (CI) = 0.792, 2.371, p = 0.264; rs1799978: OR 1.27, 95 % CI 0.511, 3.182, p = 0.603].
  
  
  CONCLUSIONS
  Despite an association of BDNF rs6265 and DRD2 rs1799978 with addictive behaviors, these variants were not associated with continued illicit opioid use in patients treated with methadone. Problematic use of opioids throughout treatment with methadone may be attributed to nongenetic factors or a polygenic effect requiring further exploration. Additional research should focus on investigating these findings in larger samples and different populations.
authors.affiliation: MiNDS Neuroscience Program, McMaster University, Hamilton, ON, Canada. baworm@mcmaster.ca.|Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada. baworm@mcmaster.ca.|Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. baworm@mcmaster.ca.
authors.forename: Monica
authors.initials: M
authors.lastname: Bawor
authors.affiliation: Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada. dennisbb@mcmaster.ca.|Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. dennisbb@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. dennisbb@mcmaster.ca.
authors.forename: Brittany B
authors.initials: BB
authors.lastname: Dennis
authors.affiliation: Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada. tancy3@mcmaster.ca.
authors.forename: Charlie
authors.initials: C
authors.lastname: Tan
authors.affiliation: Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada. pareg@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. pareg@mcmaster.ca.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. pareg@mcmaster.ca.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Canadian Addiction Treatment Centres (CATC), Richmond Hill, ON, Canada. MVarenbut@canatc.ca.
authors.forename: Michael
authors.initials: M
authors.lastname: Varenbut
authors.affiliation: Canadian Addiction Treatment Centres (CATC), Richmond Hill, ON, Canada. jdaiter@toxpro.ca.
authors.forename: Jeff
authors.initials: J
authors.lastname: Daiter
authors.affiliation: Canadian Addiction Treatment Centres (CATC), Richmond Hill, ON, Canada. cplater@toxpro.ca.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Plater
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. worster@mcmaster.ca.|Canadian Addiction Treatment Centres (CATC), Richmond Hill, ON, Canada. worster@mcmaster.ca.|Department of Medicine, McMaster University, Hamilton, ON, Canada. worster@mcmaster.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worster
authors.affiliation: Canadian Addiction Treatment Centres (CATC), Richmond Hill, ON, Canada. dmarsh@nosm.ca.|Northern Ontario School of Medicine, Laurentian Campus, Sudbury, ON, Canada. dmarsh@nosm.ca.
authors.forename: David C
authors.initials: DC
authors.lastname: Marsh
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada. mst@mcmaster.ca.|Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. mst@mcmaster.ca.|Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada. mst@mcmaster.ca.
authors.forename: Meir
authors.initials: M
authors.lastname: Steiner
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada. anglinr@mcmaster.ca.|Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada. anglinr@mcmaster.ca.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Anglin
authors.affiliation: Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada. dipika.desai@phri.ca.
authors.forename: Dipika
authors.initials: D
authors.lastname: Desai
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. thabanl@mcmaster.ca.|Biostatistics Unit, Centre for Evaluation of Medicine, Hamilton, ON, Canada. thabanl@mcmaster.ca.|System Linked Research Unit, Hamilton, ON, Canada. thabanl@mcmaster.ca.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: MiNDS Neuroscience Program, McMaster University, Hamilton, ON, Canada. samaanz@mcmaster.ca.|Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada. samaanz@mcmaster.ca.|Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. samaanz@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. samaanz@mcmaster.ca.|Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada. samaanz@mcmaster.ca.|Mood Disorders Program, St. Joseph's Healthcare Hamilton, 100 West 5th St., Hamilton, ON, L8N 3K7, Canada. samaanz@mcmaster.ca.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Samaan
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002170:Canada; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000235:genetics* / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012044:Regression Analysis; D012959:Socioeconomic Factors; D015813:Substance Abuse Detection
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C579455:BDNF protein, human; D008691:Methadone