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Sci Rep. 2014 Jan 8;4:3595. doi: 10.1038/srep03595.

Mutation in ST6GALNAC5 identified in family with coronary artery disease.

Author information

1
1] School of Biology, College of Science, University of Tehran, Tehran, Iran [2] Genome Analysis, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany [3].
2
Department of Interventional Cardiology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
3
Genome Analysis, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany.
4
School of Biology, College of Science, University of Tehran, Tehran, Iran.
5
Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
6
Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
7
Illumina, San Diego, California, USA.
8
1] School of Biology, College of Science, University of Tehran, Tehran, Iran [2] Dept. of Biotechnology, College of Science, University of Tehran, Tehran, Iran.

Abstract

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.

PMID:
24399302
PMCID:
PMC3884232
DOI:
10.1038/srep03595
[Indexed for MEDLINE]
Free PMC Article
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