Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects.

ABSTRACT: The presynaptic alpha2C adrenergic receptors (AR) act to inhibit norepinephrine release in cardiac and other presynaptic nerves. We have recently shown that a genetic variant in the alpha2CAR coding region (Del322-325), which renders the receptor partially uncoupled from Gi, is a risk factor for heart failure. However, variability of heart failure phenotypes and a dominance of Del322-325 in those of African descent led us to hypothesize that other regions of this gene have functional polymorphisms. In a multiethnic population, we found 20 polymorphisms within 4,625 bp of contiguous sequence of this intronless gene encompassing the promoter, 5' UTR, coding, and 3' UTR. These polymorphisms occur in 24 distinct haplotypes with complex organizations, including multiple 5'-upstream polymorphism

SUBMITTER: Small KM 

PROVIDER: S-EPMC516511 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature