Rare, Damaging DNA Variants in CORIN and Risk of Coronary Artery Disease: Insights From Functional Genomics and Large-Scale Sequencing Analyses.

ABSTRACT:

Background

Corin is a protease expressed in cardiomyocytes that plays a key role in salt handling and intravascular volume homeostasis via activation of natriuretic peptides. It is unknown if Corin loss-of-function (LOF) is causally associated with risk of coronary artery disease (CAD).

Methods

We analyzed all coding CORIN variants in an Italian case-control study of CAD. We functionally tested all 64 rare missense mutations in Western Blot and Mass Spectroscopy assays for proatrial natriuretic peptide cleavage. An expanded rare variant association analysis for Corin LOF mutations was conducted in whole exome sequencing data from 37 799 CAD cases and 212 184 controls.

Results

We observed LOF variants in CORIN in 8 of 1803 (0.4%) CAD cases versus 0 of 172

SUBMITTER: Wang M 

PROVIDER: S-EPMC8555653 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature