Genetic and functional association of <it>FAM5C </it>with myocardial infarction

• Main Authors: Crossman David C (Author), Seo David (Author), Haynes Carol (Author), Wang Ty (Author), Lou Xuemei (Author), Hale A Brent (Author), Crosslin David R (Author), Nelson Sarah (Author), Gadson Shera (Author), Doss Jennifer F (Author), Shah Svati H (Author), Connelly Jessica J (Author), Mooser Vincent (Author), Granger Christopher B (Author), Jones Christopher JH (Author), Kraus William E (Author), Hauser Elizabeth R (Author), Gregory Simon G (Author)
• Format: Book
• Published: BMC, 2008-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>Polymorphisms were identified within the 'family with sequence similarity 5, member C' gene (<it>FAM5C</it>) 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 <it>FAM5C</it>. <it>FAM5C </it>genotypes were also correlated with expression of the gene in human aorta. Expression levels of <it>FAM5C </it>decreased with increasing passage of proliferating aortic smooth muscle cells (SMC) suggesting a role for this molecule in smooth muscle cell proliferation and senescence.</p> <p>Conclusion</p> <p>These data implicate <it>FAM5C </it>alleles in the risk of myocardial infarction and suggest further functional studies of <it>FAM5C </it>are required to identify the gene's contribution to atherosclerosis.</p>

Item Description

10.1186/1471-2350-9-33
1471-2350