title: Mutation in ST6GALNAC5 identified in family with coronary artery disease.
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.
authors.affiliation: 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].
authors.forename: Kolsoum
authors.initials: K
authors.lastname: InanlooRahatloo
authors.affiliation: Department of Interventional Cardiology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Amir Farhang Zand
authors.initials: AF
authors.lastname: Parsa
authors.affiliation: Genome Analysis, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Huse
authors.affiliation: School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Paniz
authors.initials: P
authors.lastname: Rasooli
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Davaran
authors.affiliation: Genome Analysis, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Illumina, San Diego, California, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Illumina, San Diego, California, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Turk
authors.affiliation: Illumina, San Diego, California, USA.
authors.forename: Sasan
authors.initials: S
authors.lastname: Amini
authors.affiliation: Illumina, San Diego, California, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Steemers
authors.affiliation: Illumina, San Diego, California, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gunderson
authors.affiliation: Illumina, San Diego, California, USA.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ronaghi
authors.affiliation: 1] School of Biology, College of Science, University of Tehran, Tehran, Iran [2] Dept. of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012799:Sialyltransferases / Q000235:genetics*
chemical_list: D012799:Sialyltransferases; C400189:brain-specific GD1alpha synthase, ST6GalNAc V