Insertion/deletion polymorphism in alpha2-adrenergic receptor gene is a genetic risk factor for sudden cardiac death.
BACKGROUND
Adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. A deletion variant of the human alpha(2B)-adrenoreseptor of glutamic acid residues has been associated with impaired receptor desensitization. This receptor variant could, therefore, be involved in cardiovascular diseases associated with enhanced vasoconstriction. Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha(2B)-adrenoceptor gene is associated with the risk for sudden cardiac death.


METHODS
This was a prospective population-based study investigating risk factors for cardiovascular diseases in middle-aged men from 42 to 60 years from eastern Finland. The study is based on 1,606 men with complete data on DNA observed for an average time of 17 years.


RESULTS
In this study population, 338 men (21%) had the D/D genotype, 467 (29%) had the I/I genotype, and 801 (50%) had a heterozygous genotype. There were 76 sudden cardiac deaths during follow-up (0.81 deaths/1,000 persons per year). In a Cox model adjusting for other coronary risk factors (age, systolic blood pressure, smoking, diabetes, serum low-density lipoprotein and high-density lipoprotein cholesterol, body mass index, and exercise-induced myocardial ischemia), men with the D/D or I/D genotype had 1.97 times (95% CI 1.08-3.59, P = .026) higher risk to experience sudden cardiac death (20 events for D/D genotype, 13 events for I/I genotype, and 43 events for I/D genotype) compared with men carrying the I/I genotype. In addition, the alpha(2B)-adrenoceptor D/D genotype was associated with the risk of coronary heart disease death and acute coronary events, after adjusting for risk factors.


CONCLUSIONS
The genetic polymorphism of the alpha(2B)-adrenoreceptor is genetic risk predictor for sudden cardiac death.
Laukkanen
Jari A
JA
Research Institute of Public Health, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland. jariantero.laukkanen@uku.fi
Mäkikallio
Timo H
TH
Kauhanen
Jussi
J
Kurl
Sudhir
S
D000328:Adult; D003327:Coronary Disease / Q000097:blood / Q000235:genetics / Q000401:mortality*; D004247:DNA / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate
C547771:ADRA2B protein, human; D018341:Receptors, Adrenergic, alpha-2; D004247:DNA