title: GAD2 gene sequence variations are associated with eating behaviors and weight gain in women from the Quebec family study.
abstract: The glutamate decarboxylase 2 (GAD2) gene encodes for the glutamic acid decarboxylase enzyme (GAD65), which is implicated in the formation of the gamma-aminobutyric acid (GABA), a neurotransmitter involved in the regulation of food intake. The objective of the present study was to test for association between GAD2 single-nucleotide polymorphisms (SNPs) and eating behaviors, dietary intake and obesity in subjects (n=873) from the Quebec Family Study (QFS). Energy and macronutrient intakes were measured using a 3-day dietary record and eating behaviors were assessed using the Three-Factor Eating Questionnaire (TFEQ). Six SNPs capturing about 90% of GAD2 gene variability were genotyped and tested for association with age- and BMI- adjusted phenotypes. No evidence of association was found in men. In women, a SNP (rs992990; c.61450 C>A) was associated with disinhibition (p=0.028), emotional susceptibility to disinhibition (p=0.0005) and susceptibility to hunger (p=0.028). Another SNP (rs7908975; c.8473A>C) was associated with carbohydrate (p=0.021) and lipid (p=0.021) intakes, disinhibition (p=0.011) and two of its subscales (emotional and situational susceptibility) as well as with avoidance of fattening foods (p=0.036). Six-year weight gain was two times higher in women carrying the variants associated with eating behaviors: 4.2kg (vs 2.1kg in non-carriers) in A-allele carriers of c.61450 C>A (p=0.038) and 4.9kg (vs 2.5kg in non-carriers) in C-allele carriers of c. 8473 A>C (p=0.013). The results suggest a role for the GAD2 gene in determining food intake, eating behaviors and weight gain over time in women.
authors.affiliation: Division of kinesiology, Department of Social and Preventive Medicine, Laval University, Quebec, Canada.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Choquette
authors.forename: Simone
authors.initials: S
authors.lastname: Lemieux
authors.forename: Angelo
authors.initials: A
authors.lastname: Tremblay
authors.forename: Vicky
authors.initials: V
authors.lastname: Drapeau
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
mesh_terms: D000328:Adult; D000886:Anthropometry / Q000379:methods; D015992:Body Mass Index; D019587:Dietary Supplements; D004435:Eating / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006801:Humans; D006815:Hunger; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011792:Quebec; D011795:Surveys and Questionnaires; D015430:Weight Gain / Q000235:genetics*
chemical_list: D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2