title: Influence of Dopaminergic System Genetic Variation and Lifestyle Factors on Excessive Alcohol Consumption.
abstract: OBJECTIVE
  To examine the role of genetic and environmental factors in the pathogenesis of alcohol dependence in a Spanish cohort of women and men.
  
  
  METHODS
  We analyzed the relationship between 56 genetic variants in 7 genes associated with the dopaminergic reward pathway and excessive alcohol consumption. The study sample (N = 1533, of which 746 were women) consisted of 653 heavy consumers and 880 very low consumers from the Spanish subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. Lifestyle variables were also examined to assess associations between genetic and environmental factors.
  
  
  RESULTS
  No statistically significant differences were found between cases and controls for the allele frequencies in five genes: TH, SLC18A2, DRD1, DRD3 and COMT. Conversely, some alleles of the 12 SNPs from the DRD2 locus and the 5 from the MAOA locus showed significant associations with excessive alcohol consumption. Namely, rs10891556 (DRD2) proved to be the only SNP positively correlated with excessive alcohol consumption in both sexes. DRD2 rs1800497 and rs877138 were significantly associated in men, whereas DRD2 rs17601612 and rs4936271 and MAOA rs5906898 were associated with excessive alcohol consumption in women. A correspondence analysis provided an overall lifestyle profile of excessive drinkers, who were predominantly men who smoked, had large intakes of meat, small intakes of fruit and vegetables, whose jobs did not require high education levels and who engaged in little physical activity.
  
  
  CONCLUSIONS
  It has shown the influence of dopaminergic pathway in the genetics of alcohol dependence with differences between men and women and providing a lifestyle profile of excessive drinkers.
authors.affiliation: BIOMICs Research Group, 'Lucio Lascaray' Center for Research and Advanced Studies (CIEA), University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Celorrio
authors.affiliation: Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain Unit of Nutrition, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Muñoz
authors.affiliation: Public Health Division of Gipuzkoa, Department of Health of the Regional Government of the Basque Country, Donostia, Spain BIODonostia Research Institute, San Sebastián, Spain CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: Public Health Division of Gipuzkoa, Department of Health of the Regional Government of the Basque Country, Donostia, Spain BIODonostia Research Institute, San Sebastián, Spain CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.affiliation: Departmenet of Gastroenterology, Donostia Hospital-Instituto Biodonostia, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), San Sebastian, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Andalusian School of Public Health, Granada, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Andalusian School of Public Health, Granada, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Molina-Montes
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Department of Epidemiology, Murcia Health Council, Murcia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Department of Epidemiology, Murcia Health Council, Murcia, Spain.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Department of Epidemiology, Murcia Health Council, Murcia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: MaríaHuerta
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Public Health Institute of Navarra, Pamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain Public Health Institute of Navarra, Pamplona, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.affiliation: Public Health and Health Planning Directorate, Asturias, Spain.
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: Unit of Nutrition, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
authors.affiliation: Departmenet of Gastroenterology, Donostia Hospital-Instituto Biodonostia, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), San Sebastian, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hijona
authors.affiliation: Departmenet of Gastroenterology, Donostia Hospital-Instituto Biodonostia, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), San Sebastian, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Herreros-Villanueva
authors.affiliation: Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain Unit of Nutrition, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.affiliation: BIOMICs Research Group, 'Lucio Lascaray' Center for Research and Advanced Studies (CIEA), University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alfonso-Sánchez
authors.affiliation: BIOMICs Research Group, 'Lucio Lascaray' Center for Research and Advanced Studies (CIEA), University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain marian.mdepancorbo@ehu.es.
authors.forename: Marian M
authors.initials: MM
authors.lastname: de Pancorbo
mesh_terms: D000437:Alcoholism / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D000483:Alleles; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D059290:Dopaminergic Neurons / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics; D012201:Reward; D012727:Sex Characteristics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C583260:DRD1 protein, human; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase