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Obesity is associated with genetic variants that alter dopamine availability.

Need, AC, Ahmadi, KR, Spector, TD and Goldstein, DB (2006) Obesity is associated with genetic variants that alter dopamine availability. Ann Hum Genet, 70 (Pt 3). pp. 293-303.

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Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a well-characterized functional variant. Here we look at these four functional polymorphisms together, to investigate how heritable variation in dopamine levels influences the risk of obesity in a cohort of 1150, including 240 defined as obese (BMI > or = 30). The COMT and SLC6A3 polymorphisms showed no association with either weight, BMI or obesity risk. We found, however, that both MAOA and MAOB show an excess of the low-activity genotypes in obese individuals (MAOA:chi2= 15.45, p = 0.004; MAOB:chi2= 8.05, p = 0.018). Additionally, the MAOA genotype was significantly associated with both weight (p = 0.0005) and BMI (p = 0.001). When considered together, the 'at risk genotype'--low activity genotypes at both the MAOA and MAOB loci--shows a relative risk for obesity of 5.01. These results have not been replicated and, given the experience of complex trait genetics, warrant caution in interpretation. In implicating both the MAOA and MOAB variants, however, this study provides the first indication that dopamine availability (as opposed to other effects of MAOA) is involved in human obesity. It is therefore a priority to assess the associations in replication datasets.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Need, AC
Spector, TD
Goldstein, DB
Date : May 2006
DOI : 10.1111/j.1529-8817.2005.00228.x
Uncontrolled Keywords : Body Mass Index, Body Weight, Catechol O-Methyltransferase, Dopamine, Dopamine Plasma Membrane Transport Proteins, Genetic Predisposition to Disease, Genotype, Humans, Monoamine Oxidase, Obesity, Polymorphism, Genetic
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 24 Jan 2020 17:42

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