Abstract 4414: DNA Variations in Voltage-gated Calcium Channel Beta 2 Subunit (CACNB2) Gene, Functional Consequences, and Association with Adverse Cardiovascular Outcomes in the INternational VErapamil SR-trandolapril STudy-GENEtic Substudy

Background: Genetic variations in the CACNB2 gene, which encodes a regulatory subunit of the L-type calcium channel, have not been thoroughly characterized. We undertook a single nucleotide polymorphism (SNP) discovery effort to characterize SNPs in CACNB2 and to determine if these SNPs were associated with adverse cardiovascular outcomes in patients with hypertension and coronary artery disease (CAD), and if associated, to determine functional underpinnings. Methods: Genomic DNA from 60 ethnically diverse individuals was used for SNP discovery. SNPs from exons, intron/exon junctions, 5′ and 3′UTR of CACNB2 were identified and characterized by direct DNA sequencing. Four common SNPs (rs12764271, rs7069292, rs16917273, and rs2357928) from the 14 SNPs that were predicted to be functional by PolyMApr, were selected for a clinical association study in 1032 hypertensive CAD patients in INVEST-GENES who were randomized to atenolol or verapamil-SR-based treatment. Reporter assays were performed in CHO and HEK293...