Polymorphism of the α_2A-Adrenergic Receptor Gene and Epinephrine-Induced Platelet Aggregation.

The α_2A-adrenergic receptor mediates important physiologic responses, such as regulation of blood pressure, control of sympathetic autonomic responses, as well as the platelet response to epinephrine. The gene encoding the α_2A-adrenergic receptor is polymorphic. One of the polymorphisms, known as the Dra I polymorphism, is located in the 3′ untranslated region of this gene. The Dra I polymorphism of the α_2A-adrenergic receptor is associated with a higher incidence of systemic arterial hypertension among African-Americans. Although the presence of this polymorphism was known by Southern-blot analysis of the human genomic DNA for more than a decade, the exact location and nature of this polymorphism was unknown. We have located the Dra I polymorphism in the 3′ untranslated region of the α_2A-adrenergic receptor gene (G₁₈₃₈A) and developed a PCR-based detection method. The allele and haplotype frequencies for polymorphisms of the α_2A-adrenergic receptor gene in different ethnic groups were identified. After studying the correlation between epinephrine-induced platelet aggregation and the genotypes for the G₁₈₃₈A polymorphism among 235 human subjects, it was found that the 1838G allele is associated with an increase in the level of platelet aggregation in response to epinephrine among African-Americans, but not among Caucasians or Hispanics. This polymorphism may be responsible for the variability in the epinephrine-induced platelet aggregation among individuals and acts as a risk factor for thrombotic vascular event.