Abstract
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.
Similar content being viewed by others
References
Poston W.S.C., Foreyt J.P., Borrell L., Haddock C.K.: Challenges in obesity management. South Med. J., 91, 710–720, 1998.
Stunkard A.J.: Current views on obesity. Am. J. Med., 100, 230–236, 1996.
Greenberg D.A.: Linkage analysis of “necessary” disease loci versus “susceptibility” loci. Am. J. Hum. Genet., 52, 135–143, 1993.
Bouchard C., Pérusse L.: Current status of the human obesity gene map. Obes. Res., 4, 81–90, 1996.
Comuzzie A.G., Allison D.B.: The search for the human obesity genes. Science, 280, 1374–1377, 1998.
Comings D.E., Flanagan S.D., Dietz G., Muhleman D., Knell E., Gysin R.: The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem. Med. Metab. Biol., 50, 176–185, 1993.
Ericsson M., Poston W.S.C., Foreyt J.P.: Common biological pathways in eating disorders and obesity. Addict. Behav., 21, 733–743, 1996.
Noble E.P., Noble R.E., Ritchie T., Syndulko K., Bohlman M.C., Noble L.A., Zhang Y., Sparkes R.S., Grandy D.K.: D2 dopamine receptor gene and obesity. Int. J. Eating Disord., 15, 205–217, 1994.
Noble E.P., Fitch R.J., Ritchie T., Brunner R.L., Zhang X., St. Jeor S.C., Syndulko K., Sparkes R.S.: The D2 dopamine receptor gene: Obesity, smoking, and mood. In: St. Jeor S.T. (Ed.), Obesity assessment: Tools, methods, interpretations. New York, Chapman & Hall, 1997, pp. 522–533.
Blum K., Braverman E.R., Wood R.C., Gill J., Li C., Chen T.J., Taub M., Montgomery A.R., Sheridan P.J., Cull J.G.: Increased prevalence of the Taq I allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: A preliminary report. Pharmacogenetics, 6, 297–305, 1996.
Comings D.E., Gade R., MacMurray J.P., Muhleman D., Peters W.R.: Genetic variants of the human obesity (OB) gene: Association with body mass index in young women, psychiatric symptoms, and interaction with the dopamine D2 receptor (DRD2) gene. Mol. Psychiatry, 1, 325–335, 1996.
Lerman C., Caporaso N., Main D., Audrain J., Boyd N.R., Bowman E.D., Shields P.G.: Depression and self-medication with nicotine: The modifying influence of the do — pamine D4 receptor gene. Health Psychol., 17, 56–62, 1998.
Björvell H., Edman G., Rössner S., Schalling D.: Personality traits in a group of severely obese patients: A study of patients in two self-chosen weight reducing programs. Int. J. Obes. Relat. Metab. Disord., 9, 257–266, 1985.
Poston W.S.C., Ericsson M., Linder J., Nilsson T., Goodrick K., Foreyt J.P.: Personality and the prediction of weight loss and relapse in the treatment of obesity. Int. J. Eating Disord., in press.
Benjamin J., Li L., Patterson C., Greenberg B.D., Murphy D.L., Hamer D.H.: Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat. Genet., 12, 81–84, 1996.
Ebstein R.P., Novick O., Umansky R., Priel B., Osher Y., Blaine D., Bennett E.R., Nemanov L., Katz M., Belmaker R.H.: Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat. Genet., 12, 78–80, 1996.
Ebstein R.P., Nemanov L., Klotz I., Gritsenko I., Belmaker R.H.: Additional evidence for an association between the dopamine D4 receptor (D4DR) exon III repeat polymorphism and the human personality trait of Novelty Seeking. Mol. Psychiatry, 2, 472–477, 1997.
Jönsson E.G., Nöthen M.M., Gustavsson J.P., Neidt H., Brené S., Tylec A., Propping P., Sedvall G.C.: Lack of evidence for allelic association between personality traits and the dopamine D4 receptor gene polymorphisms. Am. J. Psychiatry, 154, 697–699, 1997.
Jönsson E.G., Nöthen M.M., Gustavsson J.P., Neidt H., Forslund K., Mattila-Evenden M., Rylander G., Propping P., Åsberg M.: Lack of association between dopamine D4 receptor gene and personality traits. Psychol. Med., in press.
Malhotra A.K., Virkkunen M., Rooney W., Eggert E., Linnoila M., Goldman D.: The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and Novelty Seeking. Mol. Psychiatry, 1, 388–391, 1996.
Gelernter J., Kranzler H., Coccaro E., Siever L., New A., Mulgrew C.L.: D4 dopaminereceptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects. Am. J. Hum. Genet., 61, 1144–1152, 1997.
Sander T., Harms H., Dufeu P., Kuhn S., Rommelspacher H., Schmidt L.G.: Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics. Am. J. Med. Genet., 74, 483–487, 1997.
Vandenbergh D.J., Zonderman A.B., Wang J., Uhl G.R., Costa Jr P.T.: No association between novelty seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore Longitudinal Study of Aging participants. Mol. Psychiatry, 2, 417–419, 1997.
Sullivan P.F., Fifield W.J., Kennedy M.A., Mulder R.T., Sellman J.D., Joyce P.R.: No association between novelty seeking and the type 4 dopamine receptor gene (DRD4) in two New Zealand samples. Am. J. Psychiatry, 155, 98–101, 1998.
Pogue-Geile M., Ferrell R., Deka R., Debski T., Manuck S.: Human Novelty Seeking personality traits and dopamine D4 receptor polymorphisms: a twin and genetic association study. Am. J. Med. Genetics, 81, 44–48, 1998.
Schalling D., Edman G.: The Karolinska Scales of Personality (KSP) Manual: An inventory for assessing temperament dimensions associated with vulnerability for psychosocial deviance. Stockholm, Sweden, Department of Psychiatry, Karolinska Institute, 1993.
Schalling D., Åsberg M., Edman G., Oreland L.: Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity. Acta Psychiatr. Scand., 76, 172–182, 1987.
Ekselius L., Hetta J., von Knorring L.: Relationship between personality traits as determined by means of the Karolinska Scales of Personality (KSP) and personality disorders according to DSM-III-R. Personality and Individual Differences, 16, 589–595, 1994.
Gustavsson J.P., Weinryb R.M., Göransson S., Pedersen N.L., Åsberg M.: Stability and predictive ability of personality traits across 9 years. Personality and Individual Differences, 22, 783–791, 1997.
Nordstöm P., Schalling D., Åsberg M.: Temperamental vulnerability in attempted suicide. Acta Scand. Psychiatr., 92, 155–160, 1995.
Schalling D.: Neurochemical correlates of personality, impulsivity, and disinhibitory suicidality. In: Hodgins S. (Ed.), Mental disorder and crime. New York, Sage Publications, 1993, pp. 208–226.
Blackburn G.L., Kanders B.S.: Medical evaluation and treatment of the obese patient with cardiovascular disease. Am. J. Cardiol., 60, 55G–58G, 1987.
Whitaker R.C., Wright J.A., Pepe M.S., Seidel K.D., Dietz W.H. Predicting obesity in young adulthood from childhood and parental obesity. N. Engl. J. Med., 337, 869–873, 1997.
Roth H., Hinney A., Ziegler A., Barth N., Gerber G., Stein K., Bromel T., Mayer H., Siegfried W., Schafer H., Remschmidt H., Grzeschik K.H., Hebebrand J.: Further support for linkage of extreme obesity to the obese gene in a study group of obese children and adolescents. Exp. Clin. Endocrinol. Diabetes, 105, 341–344, 1997.
Halpern A., Neves M.Q., Marsiaj H.I., Bernik M.M.: Survey of obesity onset in patients applying for a weight reduction program. Diabetes Res. Clin. Pract., 10 (Suppl 1), S77–S79, 1990.
Noble R.E.: The incidence of parental history of obesity in overweight individuals. Int. J. Eating Disord., 22, 265–271, 1997.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poston, W.S.C., Ericsson, M., Linder, J. et al. D4 dopamine receptor gene exon III polymorphism and obesity risk. Eat Weight Disord 3, 71–77 (1998). https://doi.org/10.1007/BF03339991
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03339991