The catecholamine biosynthetic enzyme dopamine β-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter.

ABSTRACT: Dopamine beta-hydroxylase (DBH) is the biosynthetic enzyme catalyzing formation of norepinephrine. Changes in DBH expression or activity have been implicated in the pathogenesis of cardiovascular and neuropsychiatric disorders. Genetic determination of DBH enzymatic activity and its secretion are only incompletely understood. We began with a genome-wide association search for loci contributing to DBH activity in human plasma. Initially, in a population sample of European ancestry, we identified the proximal DBH promoter as a region harboring three common trait-determining variants (top hit rs1611115, P = 7.2 × 10(-51)). We confirmed their effects on transcription and showed that the three variants each acted additively on gene expression. Results were replicated in a population sample of N

SUBMITTER: Mustapic M 

PROVIDER: S-EPMC4222356 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature