LRP6 Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors

Overview

Journal Science

Specialty Science

Date 2007 Mar 3

PMID 17332414

Citations 309

Authors

Arya Mani

Jayaram Radhakrishnan

He Wang

Alaleh Mani

Mohammad-Ali Mani

Carol Nelson-Williams

Khary S Carew

Shrikant Mane

Hossein Najmabadi

Dan Wu

Richard P Lifton

Affiliations

Soon will be listed here.

Abstract

Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.

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