An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events.
OBJECTIVE
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.
Snapir
A
A
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Heinonen
P
P
Tuomainen
T P
TP
Alhopuro
P
P
Karvonen
M K
MK
Lakka
T A
TA
Nyyssönen
K
K
Salonen
R
R
Kauhanen
J
J
Valkonen
V P
VP
Pesonen
U
U
Koulu
M
M
Scheinin
M
M
Salonen
J T
JT
D000704:Analysis of Variance; D001794:Blood Pressure; D003327:Coronary Disease / Q000097:blood / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D017353:Gene Deletion; D005808:Genes, Recessive / Q000235:genetics; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011159:Population Surveillance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis
C547771:ADRA2B protein, human; C547772:Adra2b protein, mouse; D018341:Receptors, Adrenergic, alpha-2