Clinical study: risk factors
An insertion/deletion polymorphism in the α2b-adrenergic receptor gene is a novel genetic risk factor for acute coronary events

https://doi.org/10.1016/S0735-1097(01)01201-3Get rights and content
Under an Elsevier user license
open archive

Abstract

OBJECTIVES

Our aim was to study whether an insertion/deletion (I/D) polymorphism in the α2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.

BACKGROUND

α2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The α2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human α2B-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 α2B-adrenoceptor genotype was not associated with hypertension in this study population.

CONCLUSIONS

The D/D genotype of the α2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Abbreviations

AMI
acute myocardial infarction
AR
adrenergic receptor
BMI
body mass index
BP
blood pressure
CHD
coronary heart disease
CI
confidence interval
D
deletion
ECG
electrocardiogram
I
insertion
KIHD
Kuopio Ischemic Heart Disease Risk Factor study
LDL
low density lipoprotein
PCR
polymerase chain reaction
RR
relative risk
WHO
World Health Organization

Cited by (0)

Support for this study was provided by the European Commission (BMH4-CT98-373), Turku University Hospital and by research grants from the National Heart, Lung and Blood Institute of the U.S. (grant HL 44199 to Dr. George A. Kaplan) and the Academy of Finland (grants 41471, 1041086 and 2041022 to Dr. Jukka T. Salonen). Dr. Heinonen was supported by the Research and Science Foundation of Farmos and the Yrjö Jahnsson Foundation.