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Genetic and functional association of FAM5C with myocardial infarction

Connelly, J., Shah, S., Doss, J., Gadson, S., Nelson, S., Crosslin, D., Hale, A.B., Lou, X., Wang, T., Haynes, C., Seo, D., Crossman, D., Mooser, V., Granger, C., Jones, C., Kraus, W., Hauser, E. and Gregory, S. (2008) Genetic and functional association of FAM5C with myocardial infarction. BMC Medical Genetics, 9 (1). p. 33. ISSN 1471-2350

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Abstract

BACKGROUND:

We 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.

METHODS:

A 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).RESULTS:Polymorphisms 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 of FAM5C. FAM5C genotypes were also correlated with expression of the gene in human aorta. Expression levels of FAM5C decreased with increasing passage of proliferating aortic smooth muscle cells (SMC) suggesting a role for this molecule in smooth muscle cell proliferation and senescence.

CONCLUSION:These data implicate FAM5C alleles in the risk of myocardial infarction and suggest further functional studies of FAM5C are required to identify the gene's contribution to atherosclerosis.

Item Type: Article
Copyright, Publisher and Additional Information: © 2008 Connelly et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield)
Depositing User: Sheffield Import
Date Deposited: 02 Oct 2009 12:30
Last Modified: 08 Oct 2009 08:55
Published Version: http://www.biomedcentral.com/1471-2350/9/33
Status: Published
Publisher: Biomed Central
Identification Number: 10.1186/1471-2350-9-33
URI: http://eprints.whiterose.ac.uk/id/eprint/9631

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