Genetic and functional association of FAM5C with myocardial infarction

被引：31

作者：

Connelly, Jessica J. ^{[1
,2
]}

Shah, Svati H. ^{[1
,2
,3
]}

Doss, Jennifer F. ^{[1
,2
]}

Gadson, Shera ^{[1
,2
]}

Nelson, Sarah ^{[1
,2
]}

Crosslin, David R. ^{[1
,2
]}

Hale, A. Brent ^{[1
,2
]}

Lou, Xuemei ^{[1
,2
]}

Wang, Ty ^{[1
,2
]}

Haynes, Carol ^{[1
,2
]}

Seo, David ^{[4
]}

Crossman, David C. ^{[5
]}

Mooser, Vincent ^{[6
]}

Granger, Christopher B. ^{[1
,3
]}

Jones, Christopher J. H. ^{[7
]}

Kraus, William E. ^{[1
,2
,3
]}

Hauser, Elizabeth R. ^{[1
,2
]}

Gregory, Simon G. ^{[1
,2
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA

[3] Duke Univ, Med Ctr, Div Cardiol, Durham, NC USA

[4] Univ Miami, Miller Sch Med, Miami, FL 33136 USA

[5] Univ Sheffield, Sheffield, S Yorkshire, England

[6] GlaxoSmithKline, Philadelphia, PA USA

[7] Cardiff Univ, Cardiff CF4 4XN, S Glam, Wales

来源：

BMC MEDICAL GENETICS | 2008年 / 9卷

关键词：

D O I：

10.1186/1471-2350-9-33

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 genein 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.

引用

页数：15

共 59 条

[1] GOLD - Graphical Overview of Linkage Disequilibrium [J].

Abecasis, GR ;

Cookson, WOC .

BIOINFORMATICS, 2000, 16 (02) :182-183

[2]

[Anonymous], 2002, WORLD HLTH REPORT 20

[3] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[4] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[5] Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p [J].

Broadbent, Helen M. ;

Peden, John F. ;

Lorkowski, Stefan ;

Goel, Anuj ;

Ongen, Halit ;

Green, Fiona ;

Clarke, Robert ;

Collins, Rory ;

Franzosi, Maria Grazia ;

Tognoni, Gianni ;

Seedorf, Udo ;

Rust, Stephan ;

Eriksson, Per ;

Hamsten, Anders ;

Farrall, Martin ;

Watkins, Hugh .

HUMAN MOLECULAR GENETICS, 2008, 17 (06) :806-814

[6] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[7] The APL test: Extension to general nuclear families and haplotypes and examination of its robustness [J].

Chung, Ren-Hua ;

Hauser, Elizabeth R. ;

Martin, Eden R. .

HUMAN HEREDITY, 2006, 61 (04) :189-199

[8] Frequency of family history of acute myocardial infarction in patients with acute myocardial infarction [J].

Ciruzzi, M ;

Schargrodsky, H ;

Rozlosnik, J ;

Pramparo, P ;

Delmonte, H ;

Rudich, V ;

Piskorz, D ;

Negri, E ;

Soifer, S ;

LaVecchia, C .

AMERICAN JOURNAL OF CARDIOLOGY, 1997, 80 (02) :122-127

[9] Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis [J].

Clarke, Murray C. H. ;

Figg, Nichola ;

Maguire, Janet J. ;

Davenport, Anthony P. ;

Goddard, Martin ;

Littlewood, Trevor D. ;

Bennett, Martin R. .

NATURE MEDICINE, 2006, 12 (09) :1075-1080

[10] GATA2 is associated with familial early-onset coronary artery disease [J].

Connelly, Jessica J. ;

Wang, Tianyuan ;

Cox, Julie E. ;

Haynes, Carol ;

Wang, Liyong ;

Shah, Svati H. ;

Crosslin, David R. ;

Hale, A. Brent ;

Nelson, Sarah ;

Crossman, David C. ;

Granger, Christopher B. ;

Haines, Jonathan L. ;

Jones, Christopher J. H. ;

Vance, Jeffery M. ;

Goldschmidt-Clermont, Pascal J. ;

Kraus, William E. ;

Hauser, Elizabeth R. ;

Gregory, Simon G. .

PLOS GENETICS, 2006, 2 (08) :1265-1273

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