Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

被引：38

作者：

Scheffold, Thomas ^{[1
]}

Kullmann, Silke ^{[1
]}

Huge, Andreas ^{[2
]}

Binner, Priska ^{[1
]}

Ochs, Hermann R. ^{[3
]}

Schoels, Wolfgang ^{[4
,5
]}

Thale, Joachim ^{[6
]}

Motz, Wolfgang ^{[7
]}

Hegge, Franz Josef ^{[8
]}

Stellbrink, Christoph ^{[9
]}

Dorsel, Thomas ^{[10
]}

Guelker, Hartmut ^{[11
]}

Heuer, Hubertus ^{[12
]}

Dinh, Wilfried ^{[11
]}

Stoll, Monika ^{[2
]}

Haltern, Georg ^{[11
]}

机构：

[1] Univ Witten Herdecke, Inst Heart & Circulat Res, D-44227 Dortmund, Germany

[2] Univ Munster, Leibniz Inst Arteriosclerosis Res, D-48149 Munster, Germany

[3] Marienkrankenhaus Soest, Dept Internal Med, D-59494 Soest, Germany

[4] Heart Ctr Duisburg, Dept Cardiol, D-47137 Duisburg, Germany

[5] Heart Ctr Duisburg, Dept Angiol, D-47137 Duisburg, Germany

[6] Heart Ctr Osnabruck Bad Rothenfelde, Schuchtermann Klin, Dept Cardiol, D-49214 Bad Rothenfelde, Germany

[7] Klinikum Karlsburg, Heart & Diabet Ctr Mecklenburg Vorpommern, D-17495 Karlsburg, Germany

[8] St Christophorus Krankenhaus Werne, Dept Internal Med, D-59368 Werne, Germany

[9] Hosp Cardiol & Internal Intens Care, Stadt Kliniken Bielefeld Mitte, D-33604 Bielefeld, Germany

[10] Josephs Hosp Warendorf, Dept Cardiol, D-48231 Warendorf, Germany

[11] Heart Ctr Wuppertal Helios Kliniken, D-42117 Wuppertal, Germany

[12] St Johannes Hosp Dortmund, Dept Internal Med, D-44227 Dortmund, Germany

来源：

BMC CARDIOVASCULAR DISORDERS | 2011年 / 11卷

关键词：

CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; COMMON DISEASES; RISK-FACTORS; 4; SNPS; POLYMORPHISMS; REPLICATION; POPULATION; INTERHEART; LOCUS;

D O I：

10.1186/1471-2261-11-9

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease. Methods: The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts. Results: Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p < 0.0001; OR: 1.621 2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769. Conclusions: The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.

引用

页数：7

共 23 条

[1] Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest) [J].

Abdullah, K. G. ;

Li, L. ;

Shen, G. -Q. ;

Hu, Y. ;

Yang, Y. ;

MacKinlay, K. G. ;

Topol, E. J. ;

Wang, Q. K. .

ANNALS OF HUMAN GENETICS, 2008, 72 :654-657

[2] Risk factors for myocardial infarction in women and men: insights from the INTERHEART study [J].

Anand, Sonia S. ;

Islam, Shofiqul ;

Rosengren, Annika ;

Franzosi, Maria Grazia ;

Steyn, Krisela ;

Yusufali, Afzal Hussein ;

Keltai, Matyas ;

Diaz, Rafael ;

Rangarajan, Sumathy ;

Yusuf, Salim .

EUROPEAN HEART JOURNAL, 2008, 29 (07) :932-940

[3]

[Anonymous], 2007, NATURE, V447, P661, DOI DOI 10.1038/NATURE05911

[4] Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study [J].

Assimes, Themistocles L. ;

Knowles, Joshua W. ;

Basu, Analabha ;

Iribarren, Carlos ;

Southwick, Audrey ;

Tang, Hua ;

Absher, Devin ;

Li, Jun ;

Fair, Joan M. ;

Rubin, Geoffrey D. ;

Sidney, Stephen ;

Fortmann, Stephen P. ;

Go, Alan S. ;

Hlatky, Mark A. ;

Myers, Richard M. ;

Risch, Neil ;

Quertermous, Thomas .

HUMAN MOLECULAR GENETICS, 2008, 17 (15) :2320-2328

[5]

ASSMANN G, 1989, AM J CARDIOL, V63, pH33

[6] A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease [J].

Chen, Zhong ;

Qian, Qi ;

Ma, Genshan ;

Wang, Jiahong ;

Zhang, Xiaoli ;

Feng, Yi ;

Shen, Chengxing ;

Yao, Yuyu .

MOLECULAR BIOLOGY REPORTS, 2009, 36 (05) :889-893

[7] Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Artery Disease [J].

Dandona, Sonny ;

Stewart, Alexandre F. R. ;

Chen, Li ;

Williams, Kathryn ;

So, Derek ;

O'Brien, Ed ;

Glover, Christopher ;

LeMay, Michel ;

Assogba, Olivia ;

Vo, Lan ;

Wang, Yan Qing ;

Labinaz, Marino ;

Wells, George A. ;

McPherson, Ruth ;

Roberts, Robert .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 56 (06) :479-486

[8] Identifying the susceptibility genes for coronary artery disease: from hyperbole through doubt to cautious optimism [J].

Hamsten, A. ;

Eriksson, P. .

JOURNAL OF INTERNAL MEDICINE, 2008, 263 (05) :538-552

[9] The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm [J].

Helgadottir, Anna ;

Thorleifsson, Gudmar ;

Magnusson, Kristinn P. ;

Gretarsdottir, Solveig ;

Steinthorsdottir, Valgerdur ;

Manolescu, Andrei ;

Jones, Gregory T. ;

Rinkel, Gabriel J. E. ;

Blankensteijn, Jan D. ;

Ronkainen, Antti ;

Jaaskelainen, Juha E. ;

Kyo, Yoshiki ;

Lenk, Guy M. ;

Sakalihasan, Natzi ;

Kostulas, Konstantinos ;

Gottsater, Anders ;

Flex, Andrea ;

Stefansson, Hreinn ;

Hansen, Torben ;

Andersen, Gitte ;

Weinsheimer, Shantel ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Shah, Svati H. ;

Quyyumi, Arshed A. ;

Granger, Christopher B. ;

Reilly, Muredach P. ;

Austin, Harland ;

Levey, Allan I. ;

Vaccarino, Viola ;

Palsdottir, Ebba ;

Walters, G. Bragi ;

Jonsdottir, Thorbjorg ;

Snorradottir, Steinunn ;

Magnusdottir, Dana ;

Gudmundsson, Gudmundur ;

Ferrell, Robert E. ;

Sveinbjornsdottir, Sigurlaug ;

Hernesniemi, Juha ;

Niemela, Mika ;

Limet, Raymond ;

Andersen, Karl ;

Sigurdsson, Gunnar ;

Benediktsson, Rafn ;

Verhoeven, Eric L. G. ;

Teijink, Joep A. W. ;

Grobbee, Diederick E. ;

Rader, Daniel J. ;

Collier, David A. ;

Pedersen, Oluf .

NATURE GENETICS, 2008, 40 (02) :217-224

[10] A common variant on chromosome 9p21 affects the risk of myocardial infarction [J].

Helgadottir, Anna ;

Thorleifsson, Gudmar ;

Manolescu, Andrei ;

Gretarsdottir, Solveig ;

Blondal, Thorarinn ;

Jonasdottir, Aslaug ;

Jonasdottir, Adalbjorg ;

Sigurdsson, Asgeir ;

Baker, Adam ;

Palsson, Arnar ;

Masson, Gisli ;

Gudbjartsson, Daniel F. ;

Magnusson, Kristinn P. ;

Andersen, Karl ;

Levey, Allan I. ;

Backman, Valgerdur M. ;

Matthiasdottir, Sigurborg ;

Jonsdottir, Thorbjorg ;

Palsson, Stefan ;

Einarsdottir, Helga ;

Gunnarsdottir, Steinunn ;

Gylfason, Arnaldur ;

Vaccarino, Viola ;

Hooper, W. Craig ;

Reilly, Muredach P. ;

Granger, Christopher B. ;

Austin, Harland ;

Rader, Daniel J. ;

Shah, Svati H. ;

Quyyumi, Arshed A. ;

Gulcher, Jeffrey R. ;

Thorgeirsson, Gudmundur ;

Thorsteinsdottir, Unnur ;

Kong, Augustine ;

Stefansson, Kari .

SCIENCE, 2007, 316 (5830) :1491-1493

← 1 2 3 →