Absence of the α_2c-adrenoceptor Del322-325 allele is associated with increased mortality in patients with chronic systolic heart failure

Objective: The Del322-325 polymorphism of the α_2c- adrenoceptor is considered to be a possible risk factor for heart failure (HF). We investigated the possible clinical association between the presence or absence of the deletion allele and mortality. Methods and Results: Of 261 chronic systolic HF patients evaluated, 216 (83%) carried no α_2c-adrenoceptor Del322-325 alleles (designated II); 28 patients (11%) were heterozygous (ID) and 17 patients (6%) homozygous (DD) for the deletion. Similar genetic distribution of α_2c-adrenoceptor Del322-325 subgroups was found in a control group of 96 healthy individuals. Mortality was significantly higher in HF patients in whom the deletion allele was absent than in HF patients who carried it: 67 (31%) patients in the II subgroup died compared with 7 (15.5%) in the ID/DD subgroup (P =.01). The odds ratio for death in HF patients who carried no α_2c-adrenoceptor Del322-325 alleles compared with HF patients with ≥1 allele was 2.45 (95% confidence interval 1.045.74). There were no differences in other relevant clinical parameters between the 2 subgroups of HF patients. Conclusions: The mortality rate of chronic systolic HF patients carrying no α_2c- adrenoceptor Del322-325 alleles was significantly higher (almost 2.5-fold) than that of HF patients carrying ≥1 allele.