The alpha-adducin gene is associated with macrovascular complications and mortality in patients with type 2 diabetes

We examined the association between alpha-adducin 1 (ADD1) gene polymorphism (Gly460Trp) with macrovascular complications and mortality in type 2 diabetes in a Caucasian population aged >or=55 years. The study was part of the Rotterdam Study, a prospective population-based cohort study. ADD1 polymorphism was determined in 6,471 participants, including 599 patients with type 2 diabetes at baseline. The prevalence of hypertension in type 2 diabetic patients was 2.57 times higher in ADD1 TT carriers compared with GG carriers (95% CI 1.05-6.32, P = 0.03). Homozygous T carriers also had a higher mean common carotid intima media thickness (IMT) compared with GG carriers (mean difference 0.05 mm, P for trend = 0.03). In diabetic patients with hypertension, the risk of mortality was 1.83 times higher in homozygous T carriers compared with the GG genotype group (95% CI 1.07-3.16, P = 0.03). The increased risk was only present among TT carriers who did not use antidiabetes medication (hazard ratio 2.18 [95% CI 1.12-4.24], P = 0.02). The results of this population-based cohort study suggest that the ADD1 gene contributes to the risk of hypertension and increases mean common carotid IMT in patients with type 2 diabetes. Furthermore, the study indicates that the ADD1 polymorphism could be useful in identifying hypertensive type 2 diabetic patients with a high risk of mortality.