Mutation in ST6GALNAC5 identified in family with coronary artery disease

We aimed to identify the genetic cause of coronary artery disease (CAD) in an Iranian pedigree. Genetic linkage analysis identified three loci with an LOD score of 2.2. Twelve sequence variations identified by exome sequencing were tested for segregation with disease. A p.Val99Met causing mutation i...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2014-01, Vol.4 (1), p.3595-3595, Article 3595
Main Authors: InanlooRahatloo, Kolsoum, Parsa, Amir Farhang Zand, Huse, Klaus, Rasooli, Paniz, Davaran, Saeid, Platzer, Matthias, Kramer, Marcel, Fan, Jian-Bing, Turk, Casey, Amini, Sasan, Steemers, Frank, Gunderson, Kevin, Ronaghi, Mostafa, Elahi, Elahe
Format: Article
Language:English
Subjects:
13/1
13/44
45/22
45/23
45/61
45/70
45/77
631/208/2489/144
692/699/75
82/83
Adult
Amino acids
Cardiovascular disease
Case-Control Studies
Coronary artery
Coronary Artery Disease - genetics
Coronary vessels
Female
Heart diseases
Humanities and Social Sciences
Humans
Hypercholesterolemia
Linkage analysis
Male
Middle Aged
multidisciplinary
Mutation
Pedigree
Science
Sialyltransferases - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We aimed to identify the genetic cause of coronary artery disease (CAD) in an Iranian pedigree. Genetic linkage analysis identified three loci with an LOD score of 2.2. Twelve sequence variations identified by exome sequencing were tested for segregation with disease. A p.Val99Met causing mutation in ST6GALNAC5 was considered the likely cause of CAD. ST6GALNAC5 encodes sialyltransferase 7e. The variation affects a highly conserved amino acid, was absent in 800 controls and was predicted to damage protein function. ST6GALNAC5 is positioned within loci previously linked to CAD-associated parameters. While hypercholesterolemia was a prominent feature in the family, clinical and genetic data suggest that this condition is not caused by the mutation in ST6GALNAC5 . Sequencing of ST6GALNAC5 in 160 Iranian patients revealed a candidate causative stop-loss mutation in two other patients. The p.Val99Met and stop-loss mutations both caused increased sialyltransferase activity. Sequence data from combined Iranian and US controls and CAD affected individuals provided evidence consistent with potential role of ST6GALNAC5 in CAD. We conclude that ST6GALNAC5 mutations can cause CAD. There is substantial literature suggesting a relation between sialyltransferase and sialic acid levels and coronary disease. Our findings provide strong evidence for the existence of this relation.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep03595