Polymorphism in exon 6 of the dopamine D2 receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men

Journal of Human Hypertension volume 15, pages553–558(2001)Cite this article

Abstract

A deficient dopamine D2 receptor (DA2) formation or action may contribute to hypertension via an increase of catecholamine release. In addition, Axis II personality disorders that appears odd or eccentric (cluster A) is associated with a low density of DA2. This study sought to examine if a NcoI restriction fragment length polymorphism (C to T transition) in exon 6 of the dopamine D2 receptor gene (DRD2) was associated with these characteristics. The genotypes (CC, CT and TT) were compared in anthropometric, endocrine, metabolic and haemodynamic variables as well as estimates of personality disorders in 284 randomly selected 51-year-old men. Homozygotes for the C allele constituted 49% of the men and homozygotes for the T allele 9%, while heterozygotes were 41%. The TT genotype was associated with elevated systolic and diastolic blood pressure, independent of obesity and endocrine abnormalities, including the hypothalamic-pituitary-adrenal axis regulation. Moreover, the TT genotype was significantly more frequent among subjects with grade 1 (mild) hypertension (>140/90 mm Hg) compared to normotensive subjects (<130/85 mm Hg). The polymorphism in exon 6 of the DRD2 was also significantly associated with cluster A personality disorders. These results suggest that a polymorphism in exon 6 of the DRD2examined with the restriction enzyme NcoI is associated with an elevated blood pressure, independent of obesity. Paranoid or schizoid personality disorders is also associated with a polymorphism of the DRD2, which might be associated with a previously demonstrated low density of this receptor.

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References

  1. 1

    Missale C et alDopamine receptors: from structure to function Physiol Rev 1998 78 189–225

    CAS  Article  Google Scholar 

  2. 2

    Kuchel O The heterogeneity of dopamine involvement in essential hypertension Clin Exp Hypertens [A] 1989 11 (Suppl 1) 217–225

    Google Scholar 

  3. 3

    Folkow B Physiological aspects of primary hypertension Physiol Rev 1982 62 347–504

    CAS  Article  Google Scholar 

  4. 4

    van den Buuse M, Versteeg DH, de Jong W Role of dopamine in the development of spontaneous hypertension Hypertension 1984 6 899–905

    CAS  Article  Google Scholar 

  5. 5

    Linthorst AC, De Lang H, De Jong W, Versteeg DH Effect of the dopamine D2 receptor agonist quinpirole on the in vivo release of dopamine in the caudate nucleus of hypertensive rats Eur J Pharmacol 1991 201 125–133

    CAS  Article  Google Scholar 

  6. 6

    Jackson DM, Westlind-Danielsson A Dopamine receptors: molecular biology, biochemistry and behavioural aspects Pharmacol Ther 1994 64 291–370

    CAS  Article  Google Scholar 

  7. 7

    Sigmundson HK Pharmacotherapy of schizophrenia: a review Can J Psychiatry 1994 39 (Suppl 2) S70–S75

    Google Scholar 

  8. 8

    Meador-Woodruff JH Update on dopamine receptors Ann Clin Psychiatry 1994 6 79–90

    CAS  Article  Google Scholar 

  9. 9

    Farde L, Gustavsson JP, Jonsson E D2 dopamine receptors and personality traits (letter) Nature 1997 385 590

    CAS  Article  Google Scholar 

  10. 10

    Langston JW, Koller WC, Giron LT Etiology of Parkinson’s disease. In: Olanow CW, Lieberman AN (eds) The Scientific Basis for the Treatment of Parkinson’s Disease Parthenon Publishing Group: Lancs 1992 33–58

    Google Scholar 

  11. 11

    Noble EP et alD2 dopamine receptor gene and obesity Int J Eat Disord 1994 15 205–217

    CAS  Article  Google Scholar 

  12. 12

    Comings DE et alThe dopamine D2 receptor (DRD2) as a major gene in obesity and height Biochem Med Metab Biol 1993 50 176–185

    CAS  Article  Google Scholar 

  13. 13

    Hoebel BG Brain neurotransmitters in food and drug reward Am J Clin Nutr 1985 42 1133–1150

    CAS  Article  Google Scholar 

  14. 14

    Ekselius L et alSCID II interviews and the SCID Screen questionnaire as diagnostic tools for personality disorders in DSM-III-R Acta Psychiatr Scand 1994 90 120–123

    CAS  Article  Google Scholar 

  15. 15

    Rosmond R Eriksson E. Björntorp P. Personality disorders in relation to anthropometric, endocrine and metabolic factors J Endocrinol Invest 1999 22 279–288

    CAS  Article  Google Scholar 

  16. 16

    Rosmond R, Dallman MF, Björntorp P Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities J Clin Endocrinol Metab 1998 83 1853–1859

    CAS  PubMed  Google Scholar 

  17. 17

    American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders APA: Washington, DC 1994

    Google Scholar 

  18. 18

    Breier A et alDopamine D2 receptor density and personal detachment in healthy subjects Am J Psychiatry 1998 155 1440–1442

    CAS  Article  Google Scholar 

  19. 19

    Kestler LP et alThe relation between dopamine D2 receptor density and personality: preliminary evidence from the NEO personality inventory-revised Neuropsychiatry Neuropsychol Behav Neurol 2000 13 48–52

    CAS  PubMed  Google Scholar 

  20. 20

    Rosmond R, Lapidus L, Björntorp P The influence of occupational and social factors on obesity and body fat distribution in middle-aged men Int J Obes Relat Metab Disord 1996 20 599–607

    CAS  PubMed  Google Scholar 

  21. 21

    Rosmond R, Lapidus L, Mårin P, Björntorp P Mental distress, obesity and body fat distribution in middle-aged men Obes Res 1996 4 245–252

    CAS  Article  Google Scholar 

  22. 22

    Rosmond R, Lapidus L, Björntorp P A comparative review of psychosocial and occupational environment in native Swedes and immigrants Scand J Soc Med 1996 24 237–242

    CAS  Article  Google Scholar 

  23. 23

    Sjöstrom L et alThe sagittal diameter is a valid marker of the visceral adipose tissue volume. In: Angel A et al (eds) Progress in Obesity Research: 7 John Libbey & Co: London 1996 309–319

    Google Scholar 

  24. 24

    Römer M et alEuropean Multicentre Evaluation of the ESAT 6660 J Clin Chem Clin Biochem 1990 28 435–443

    PubMed  Google Scholar 

  25. 25

    Wiklund O et alAlphalipoprotein cholesterol levels in relation to acute myocardial infarction and its risk factors Scand J Clin Lab Invest 1980 40 239–247

    CAS  Article  Google Scholar 

  26. 26

    Sarkar G et alDirect sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor Genomics 1991 11 8–14

    CAS  Article  Google Scholar 

  27. 27

    Spjotvoll E, Stoline M An extension of the T-method of multiple comparison to include the cases with unequal sample sizes J Am Stat Assoc 1973 68 976–978

    Google Scholar 

  28. 28

    World Health Organization International Society of Hypertension Guidelines for the management of hypertension. Guidelines Subcommittee J Hypertens 1999 17 151–183

    Google Scholar 

  29. 29

    Serrano PA, Figueroa G, Torres MZ, Del Angel AR Adrenaline, noradrenaline and dopamine excretion inpatients with essential hypertension Am J Cardiol 1964 13 484–488

    CAS  Article  Google Scholar 

  30. 30

    Missale C et alIdentification and characterization of postsynaptic D1- and D2-dopamine receptors in the cardiovascular system J Cardiovasc Pharmacol 1988 11 643–650

    CAS  Article  Google Scholar 

  31. 31

    Foucart S et alModulation of adrenal catecholamine release by DA2 dopamine receptors in the anaesthetized dog Clin Exp Pharmacol Physiol 1988 15 601–611

    CAS  Article  Google Scholar 

  32. 32

    Amenta F et alPharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex Eur J Endocrinol 1994 131 91–96

    CAS  Article  Google Scholar 

  33. 33

    Mannelli M et alEffects of different dopaminergic antagonists on bromocriptine-induced inhibition of norepinephrine release J Clin Endocrinol Metab 1984 59 74–78

    CAS  Article  Google Scholar 

  34. 34

    Mannelli M et alEndogenous dopamine (DA) and DA2 receptors: a mechanism limiting excessive sympathetic-adrenal discharge in humans J Clin Endocrinol Metab 1988 66 626–631

    CAS  Article  Google Scholar 

  35. 35

    Rosmond R et alA glucocorticoid receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitary-adrenal axis Obes Res 2000 8 211–218

    CAS  Article  Google Scholar 

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Acknowledgements

The study was supported by grants from the Swedish Medical Research Council (K97–19X–00251–35A) and the Medical Research Council of Canada (MT-13960). The first author would also like to acknowledge the Henning and Johan Throne-Holst Foundation for the support of a postdoctoral fellowship at the Pennington Biomedical Research Center.

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Affiliations

  1. Department of Heart and Lung Diseases, Göteborg University, Göteborg, Sweden

    R Rosmond & P Björntorp

  2. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA

    R Rosmond, T Rankinen, M Chagnon & C Bouchard

  3. Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Quebec, Canada

    L Pérusse & YC Chagnon

Authors
  1. R Rosmond
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  2. T Rankinen
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  3. M Chagnon
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  4. L Pérusse
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  5. YC Chagnon
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  6. C Bouchard
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  7. P Björntorp
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Correspondence to R Rosmond.

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Rosmond, R., Rankinen, T., Chagnon, M. et al. Polymorphism in exon 6 of the dopamine D2 receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men. J Hum Hypertens 15, 553–558 (2001). https://doi.org/10.1038/sj.jhh.1001231

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Keywords

  • dopamine
  • DRD2 polymorphism
  • blood pressure
  • personality disorders
  • abdominal obesity

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