title: Two functional serotonin polymorphisms moderate the effect of food reinforcement on BMI.
abstract: Food reinforcement, or the motivation to eat, has been associated with increased energy intake, greater body weight, and prospective weight gain. Much of the previous research on the reinforcing value of food has focused on the role of dopamine, but it may be worthwhile to examine genetic polymorphisms in the serotonin and opioid systems as these neurotransmitters have been shown to be related to reinforcement processes and to influence energy intake. We examined the relationship among 44 candidate genetic polymorphisms in the dopamine, serotonin, and opioid systems, as well as food reinforcement and body mass index (BMI) in a sample of 245 individuals. Polymorphisms in the monoamine oxidase A (MAOA-LPR) and serotonin receptor 2A genes (rs6314) moderated the effect of food reinforcement on BMI, accounting for an additional 5-10% variance and revealed a potential role of the single nucleotide polymorphism, rs6314, in the serotonin 2A receptor as a differential susceptibility factor for obesity. Differential susceptibility describes a factor that can confer either risk or protection depending on a second variable, such that rs6314 is predictive of both high and low BMI based on the level of food reinforcement, while the diathesis stress or dual-gain model only influences one end of the outcome measure. The interaction with MAOA-LPR better fits the diathesis stress model, with the 3.5R/4R allele conferring protection for individuals low in food reinforcement. These results provide new insight into genes theoretically involved in obesity, and support the hypothesis that genetics moderate the association between food reinforcement and BMI.
authors.affiliation: Department of Pediatrics, University at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY 14214-3000, USA.
authors.forename: Katelyn A
authors.initials: KA
authors.lastname: Carr
authors.forename: Henry
authors.initials: H
authors.lastname: Lin
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Fletcher
authors.forename: Lara
authors.initials: L
authors.lastname: Sucheston
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Singh
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Salis
authors.forename: Richard W
authors.initials: RW
authors.lastname: Erbe
authors.forename: Myles S
authors.initials: MS
authors.lastname: Faith
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Eric
authors.initials: E
authors.lastname: Stice
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Epstein
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003216:Conditioning, Operant / Q000502:physiology; D004435:Eating / Q000235:genetics; D002149:Energy Intake / Q000502:physiology; D005260:Female; D005502:Food; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D011954:Receptors, Dopamine / Q000235:genetics; D012054:Reinforcement, Psychology; D013315:Stress, Psychological / Q000235:genetics; D011795:Surveys and Questionnaires; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D055815:Young Adult
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D011954:Receptors, Dopamine; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D002394:Catechol O-Methyltransferase
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