An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events

J Am Coll Cardiol. 2001 May;37(6):1516-22. doi: 10.1016/s0735-1097(01)01201-3.


Objectives: Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.

Background: alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction.

Methods: This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years.

Results: In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population.

Conclusions: The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Blood Pressure
  • Coronary Disease / blood
  • Coronary Disease / classification
  • Coronary Disease / epidemiology
  • Coronary Disease / genetics*
  • Finland / epidemiology
  • Gene Deletion*
  • Genes, Recessive / genetics
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Hypertension / complications
  • Hypertension / diagnosis
  • Hypertension / therapy
  • Male
  • Middle Aged
  • Mutagenesis, Insertional / genetics*
  • Polymorphism, Genetic / genetics*
  • Population Surveillance
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, Adrenergic, alpha-2 / genetics*
  • Risk Assessment
  • Risk Factors
  • Survival Analysis


  • ADRA2B protein, human
  • Adra2b protein, mouse
  • Receptors, Adrenergic, alpha-2