Genetic Polymorphisms: An Insertion/Deletion Polymorphism of the a2B-Adrenoceptor Gene as a Risk Factor for Acute Coronary Events

Abstract

BACKGROUND: We have recently identified a variant form of the human 2B-adrenoreceptor (AR) gene. Based on the coronary vasoconstrictive property of 2-adrenoreceptors in humans, we hypothesized that the naturally occurring D (deletion) variant confers reduced receptor desensitization and therefore increased vasoconstriction in humans. This property could be associated with cardiovascular pathologies such as acute myocardial infarction (AMI) and sudden cardiac death (SCD). To test this hypothesis, we carried out two separate clinical genetic studies in middle-aged Finnish men, reported in two separate original publications. METHODS: We examined a subset (912 men, aged 46 to 64 years) of the Kuopio Ischemic Heart Disease Risk Factor Study, an ongoing prospective population-based study investigating risk factors for cardiovascular diseases and related outcomes in men from eastern Finland (Prospective Follow-up study). Seven hundred out-of-hospital deaths of Finnish men in the Helsinki region were subjected to autopsy and formed the basis of the second, cross-sectional study investigating the associations between the 2B-AR I/D polymorphism and coronary heart disease (Autopsy study). DNA for genotyping was extracted using standard methods. The 2B-adrenoreceptor insertion/ deletion (I/D) genotypes were determined using PCR-amplification and DNA elec-