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Obesity is associated with genetic variants that alter dopamine availability
A C Need1, K R Ahmadi, T D Spector
1Department of Biology, University College London, The Darwin Building, Gower Street, London WC1E 6BT.
Annals of Human Genetics
|May 6, 2006
Summary
Genetic variations in dopamine-regulating enzymes monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) are linked to increased obesity risk. Low-activity genotypes in these genes suggest a significant genetic influence on body mass index (BMI) and weight.
Area of Science:
- Genetics
- Neuroscience
- Obesity Research
Background:
- Dopamine plays a role in appetite regulation, and obesity has a strong genetic component.
- Dopamine availability is influenced by COMT, MAOA, MAOB enzymes, and the SLC6A3 transporter, each with functional variants.
Purpose of the Study:
- To investigate the influence of heritable variation in dopamine levels on obesity risk by examining four functional polymorphisms.
- To analyze the association between specific gene variants and obesity, weight, and BMI.
Main Methods:
- A cohort of 1150 individuals, including 240 with obesity (BMI >= 30), was studied.
- Four functional polymorphisms in COMT, MAOA, MAOB, and SLC6A3 genes were analyzed for associations with obesity-related traits.
Main Results:
- COMT and SLC6A3 polymorphisms showed no association with weight, BMI, or obesity risk.
- Obese individuals exhibited an excess of low-activity genotypes for both MAOA and MAOB.
- MAOA genotype was significantly associated with weight and BMI; the combined low-activity genotypes of MAOA and MAOB indicated a 5.01 relative risk for obesity.
Conclusions:
- The study suggests that variations in MAOA and MAOB genes, influencing dopamine availability, are implicated in human obesity.
- These findings provide the first indication of dopamine availability's role in obesity, warranting further investigation in replication datasets.
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