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CLINICAL STUDY: CARDIAC ARREST AND PULMONARY EDEMA

Variation in the alpha_2B-adrenoceptorgene as a risk factor for prehospitalfatal myocardial infarction and sudden cardiac death

Amir Snapir, MD^*,*, Jussi Mikkelsson, MD, PhD, Markus Perola, MD, PhD, Antti Penttilä, MD, PhD, Mika Scheinin, MD, PhD^* and Pekka J. Karhunen, MD, PhD

^* Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland
UCLA Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, Los Angeles, California, USA
Department of Forensic Medicine, University of Helsinki, Helsinki, Finland

Manuscript received June 5, 2002; revised manuscript received September 23, 2002, accepted October 4, 2002.

^* Reprint requests and correspondence: Dr. Amir Snapir, Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4, FIN-20520 Turku, Finland.
snapir{at}utu.fi

OBJECTIVES: Our aim was to corroborate the observed association between the deletion/deletion (DD) genotype of the insertion/deletion polymorphism in the alpha_2B-adrenoceptor (AR) and increased risk for acute myocardial infarction (AMI), and to study whether this genotype also confers an increased risk for sudden cardiac death (SCD).

BACKGROUND: Vasospasm has been suggested to play a role in AMI. Alpha₂-AR mediate coronary vasoconstriction in humans, and studies on mice suggest the involvement of the alpha₂-AR subtype B in vasoconstriction. A deletion variant of the human alpha_2B-AR has been associated with impaired receptor desensitization in vitro. In a population-based prospective study of 912 middle-aged men, the DD genotype of the alpha_2B-AR conferred an increased risk for AMI.

METHODS: A series of 700 unselected sudden out-of-hospital deaths of middle-aged white men subjected to medico-legal autopsy was analyzed.

RESULTS: Genotype information was obtained for 683 men (DD = 22%, insertion/deletion = 51%, insertion/insertion = 27%). Carriers of the DD genotype had an increased risk for SCD (n = 278, odds ratio [OR] = 2.0, p = 0.01) and fatal AMI (n = 84, OR = 2.1, p = 0.04) compared with the other two genotypes combined. The risks for SCD and fatal AMI were higher in carriers of the DD genotype who died before the age of 55 years (OR = 4.5 and 5.0, p < 0.001 for both).

CONCLUSIONS: Middle-aged white men carrying the DD genotype of the alpha_2B-AR have a significantly increased risk for SCD and AMI, especially before the age of 55 years.

Abbreviations and Acronyms   AMI   acute myocardial infarction   AR   adrenoceptor   CHD   coronary heart disease   CI   confidence interval   DD   deletion/deletion   DNA   deoxyribonucleic acid   HSDS   Helsinki Sudden Death Study   ID   insertion/deletion   II   insertion/insertion   MI   myocardial infarction   OR   odds ratio   SCD   sudden cardiac death

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