Genetic and functional association of FAM5C with myocardial infarction

Autor: Shera Gadson, Xuemei Lou, Svati H. Shah, Vincent Mooser, David C. Crossman, Elizabeth R. Hauser, William E. Kraus, David Seo, Simon G. Gregory, Carol Haynes, Jennifer F. Doss, David R. Crosslin, A. Brent Hale, Ty Wang, Sarah C. Nelson, Christopher B. Granger, Chris Jones, Jessica J. Connelly
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Adult
Genetic Markers
Male
Acute coronary syndrome
lcsh:Internal medicine
Genotype
lcsh:QH426-470
Myocardial Infarction
Gene Expression
Single-nucleotide polymorphism
Coronary Artery Disease
030204 cardiovascular system & hematology
Biology
Polymorphism
Single Nucleotide
Muscle
Smooth
Vascular
Coronary artery disease
03 medical and health sciences
0302 clinical medicine
Framingham Heart Study
Genetic linkage
medicine
Genetics
Humans
Genetic Predisposition to Disease
Genetics(clinical)
Myocardial infarction
lcsh:RC31-1245
Aorta
Cells
Cultured
Genetics (clinical)
Aged
030304 developmental biology
0303 health sciences
Genome
Human
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis
DNA
Middle Aged
medicine.disease
DNA-Binding Proteins
lcsh:Genetics
Chromosomes
Human
Pair 1
Genetic marker
Case-Control Studies
Female
Endothelium
Vascular
Lod Score
Research Article
Genetic screen
Zdroj: BMC Medical Genetics, Vol 9, Iss 1, p 33 (2008)
BMC Medical Genetics
ISSN: 1471-2350
Popis: BackgroundWe previously identified a 40 Mb region of linkage on chromosome 1q in our early onset coronary artery disease (CAD) genome-wide linkage scan (GENECARD) with modest evidence for linkage (n = 420, LOD 0.95). When the data are stratified by acute coronary syndrome (ACS), this modest maximum in the overall group became a well-defined LOD peak (maximum LOD of 2.17, D1S1589/D1S518). This peak overlaps a recently identified inflammatory biomarker (MCP-1) linkage region from the Framingham Heart Study (maximum LOD of 4.27, D1S1589) and a region of linkage to metabolic syndrome from the IRAS study (maximum LOD of 2.59, D1S1589/D1S518). The overlap of genetic screens in independent data sets provides evidence for the existence of a gene or genes for CAD in this region.MethodsA peak-wide association screen (457 SNPs) was conducted of a region 1 LOD score down from the peak marker (168–198 Mb) in a linkage peak for acute coronary syndrome (ACS) on chromosome 1, within a family-based early onset coronary artery disease (CAD) sample (GENECARD).ResultsPolymorphisms were identified within the 'family with sequence similarity 5, member C' gene (FAM5C) that show genetic linkage to and are associated with myocardial infarction (MI) in GENECARD. The association was confirmed in an independent CAD case-control sample (CATHGEN) and strong association with MI was identified with single nucleotide polymorphisms (SNPs) in the 3' end ofFAM5C.FAM5Cgenotypes were also correlated with expression of the gene in human aorta. Expression levels ofFAM5Cdecreased with increasing passage of proliferating aortic smooth muscle cells (SMC) suggesting a role for this molecule in smooth muscle cell proliferation and senescence.ConclusionThese data implicateFAM5Calleles in the risk of myocardial infarction and suggest further functional studies ofFAM5Care required to identify the gene's contribution to atherosclerosis.
Databáze: OpenAIRE
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