Genetic and functional association of FAM5C with myocardial infarction

Jessica J. Connelly, Svati H. Shah, Jennifer F. Doss, Shera Gadson, Sarah Nelson, David R. Crosslin, A. Brent Brent, Xuemei Lou, Ty Wang, Carol Haynes, David M Seo, David C. Crossman, Vincent Mooser, Christopher B. Granger, Christopher J H Jones, William E. Kraus, Elizabeth R. Hauser, Simon G. Gregory

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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.

Original languageEnglish
Article number33
JournalBMC Medical Genetics
Volume9
DOIs
StatePublished - Apr 22 2008

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Coronary Artery Disease
Myocardial Infarction
Acute Coronary Syndrome
Genes
Smooth Muscle Myocytes
Single Nucleotide Polymorphism
Genetic Linkage
Cell Aging
Chromosomes, Human, Pair 1
Aorta
Atherosclerosis
Chromosomes
Biomarkers
Alleles
Genotype
Cell Proliferation
Genome
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

Cite this

Connelly, J. J., Shah, S. H., Doss, J. F., Gadson, S., Nelson, S., Crosslin, D. R., ... Gregory, S. G. (2008). Genetic and functional association of FAM5C with myocardial infarction. BMC Medical Genetics, 9, [33]. https://doi.org/10.1186/1471-2350-9-33

Genetic and functional association of FAM5C with myocardial infarction. / Connelly, Jessica J.; Shah, Svati H.; Doss, Jennifer F.; Gadson, Shera; Nelson, Sarah; Crosslin, David R.; Brent, A. Brent; Lou, Xuemei; Wang, Ty; Haynes, Carol; Seo, David M; Crossman, David C.; Mooser, Vincent; Granger, Christopher B.; Jones, Christopher J H; Kraus, William E.; Hauser, Elizabeth R.; Gregory, Simon G.

In: BMC Medical Genetics, Vol. 9, 33, 22.04.2008.

Research output: Contribution to journalArticle

Connelly, JJ, Shah, SH, Doss, JF, Gadson, S, Nelson, S, Crosslin, DR, Brent, AB, Lou, X, Wang, T, Haynes, C, Seo, DM, Crossman, DC, Mooser, V, Granger, CB, Jones, CJH, Kraus, WE, Hauser, ER & Gregory, SG 2008, 'Genetic and functional association of FAM5C with myocardial infarction', BMC Medical Genetics, vol. 9, 33. https://doi.org/10.1186/1471-2350-9-33
Connelly JJ, Shah SH, Doss JF, Gadson S, Nelson S, Crosslin DR et al. Genetic and functional association of FAM5C with myocardial infarction. BMC Medical Genetics. 2008 Apr 22;9. 33. https://doi.org/10.1186/1471-2350-9-33
Connelly, Jessica J. ; Shah, Svati H. ; Doss, Jennifer F. ; Gadson, Shera ; Nelson, Sarah ; Crosslin, David R. ; Brent, A. Brent ; Lou, Xuemei ; Wang, Ty ; Haynes, Carol ; Seo, David M ; Crossman, David C. ; Mooser, Vincent ; Granger, Christopher B. ; Jones, Christopher J H ; Kraus, William E. ; Hauser, Elizabeth R. ; Gregory, Simon G. / Genetic and functional association of FAM5C with myocardial infarction. In: BMC Medical Genetics. 2008 ; Vol. 9.
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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.",
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T1 - Genetic and functional association of FAM5C with myocardial infarction

AU - Connelly, Jessica J.

AU - Shah, Svati H.

AU - Doss, Jennifer F.

AU - Gadson, Shera

AU - Nelson, Sarah

AU - Crosslin, David R.

AU - Brent, A. Brent

AU - Lou, Xuemei

AU - Wang, Ty

AU - Haynes, Carol

AU - Seo, David M

AU - Crossman, David C.

AU - Mooser, Vincent

AU - Granger, Christopher B.

AU - Jones, Christopher J H

AU - Kraus, William E.

AU - Hauser, Elizabeth R.

AU - Gregory, Simon G.

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N2 - 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.

AB - 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.

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