D4 dopamine receptor gene exon III polymorphism and obesity risk

Many genes have been identified that may play a role in increasing individua susceptibility to obesity. Reduced dopamine function appears to play a role in dysfunctiona eating patterns and may predispose some individuals to obesity. The long version of the D4 dopamine receptor gene (D4DR) has been shown to alter receptor function and reduce intracellular response to dopamine. It also has been associated with novelty-seeking-related personality traits that are found with greater frequency in obese individuals. We examined the association between the long alleles of the D4DR and obesity in a sample of 115 obese patients partici pating in a weight management program. No direct relationship was found between the D4DR and body mass or novelty-seeking-related personality traits. We constructed four models o increased obesity risk that included combinations of traditional risk factors (i.e., long-term history of obesity, parental obesity, a body mass index > 40) and elevations on the novelty-seeking-related scales of the Karolinska Scales of Personality. There was a significant increase in the frequency of the D4DR long alleles in individuals defined as high risk using the combination o novelty-seeking-related personality traits, severe obesity (i.e., BMI > 40), and any other tradi tional risk factor, but not with the traditional risk factors alone. These preliminary data sugges a potential role for the D4DR gene in increasing obesity susceptibility.