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CLINICAL STUDY: RISK FACTORS

An insertion/deletion polymorphism in the _2b-adrenergic receptor gene is a novel genetic risk factor for acute coronary events

Amir Snapir, MD^*, Paula Heinonen, MD^*, Tomi-Pekka Tuomainen, MD, Pia Alhopuro, BM^*, Matti K. Karvonen, MD^*, Timo A. Lakka, MD, Kristiina Nyyssönen, PhD, Riitta Salonen, MD, Jussi Kauhanen, MD, Veli-Pekka Valkonen, BM, Ullamari Pesonen, PhD^*, Markku Koulu, MD^*, Mika Scheinin, MD^* and Jukka T. Salonen, MD

^* Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
Research Institute of Public Health, University of Kuopio, Kuopio, Finland
Inner Savo Health Center, Suonenjoki, Finland

Manuscript received May 16, 2000; revised manuscript received December 18, 2000, accepted January 29, 2001.

Reprint requests and correspondence: Dr. Jukka T. Salonen, Research Institute of Public Health, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland
jukka.salonen{at}uku.fi

OBJECTIVES

Our aim was to study whether an insertion/deletion (I/D) polymorphism in the _2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.

BACKGROUND

₂-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The ₂-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human _2B-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 _2B-adrenoceptor genotype was not associated with hypertension in this study population.

CONCLUSIONS

The D/D genotype of the _2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Abbreviations and Acronyms   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

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