Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies : The Lancet

The Lancet, Early Online Publication, 15 January 2011
doi:10.1016/S0140-6736(10)61996-4Cite or Link Using DOI
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies

Original Text
Dr Muredach P Reilly MB a b Corresponding Author †Email Address, Mingyao Li PhD c †, Jing He PhD c, Jane F Ferguson PhD a, Ioannis M Stylianou PhD b, Nehal N Mehta MD a b, Mary Susan Burnett PhD d, Joseph M Devaney PhD d, Christopher W Knouff MD e, Prof John R Thompson PhD f, Benjamin D Horne PhD h i, Alexandre FR Stewart PhD k, Themistocles L Assimes MD l, Philipp S Wild MD m, Hooman Allayee PhD n, Patrick Linsel Nitschke MD o, Riyaz S Patel MD p, Nicola Martinelli MD q, Prof Domenico Girelli MD q, Prof Arshed A Quyyumi MD p, Prof Jeffrey L Anderson MD h j, Prof Jeanette Erdmann PhD o, Alistair S Hall MD r, Prof Heribert Schunkert MD o, Prof Thomas Quertermous MD l, Prof Stefan Blankenberg MD m, Prof Stanley L Hazen PhD s, Prof Robert Roberts MD k, Sekar Kathiresan MD t u v w, Prof Nilesh J Samani MD g x, Prof Stephen E Epstein MD d, Prof Daniel J Rader MD a b, Myocardial Infarction Genetics Consortium‡Wellcome Trust Case Control Consortium‡

Summary

Background
We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.

Methods
We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644).

Findings
In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction.

Interpretation
Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD.

Funding
The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies : The Lancet




GENÉTICA
Actualidad Ultimas noticias - JANOes
Identifican variantes genéticas que predisponen a la aterosclerosis y al infarto de miocardio

JANO.es · 18 Enero 2011 15:43

El hallazgo abre una vía alternativa a la evaluación personalizada de riesgos y al desarrollo de nuevas terapias para la EAC.


Un análisis de la Universidad de Pensilvania en Filadelfia, Estados Unidos, sobre dos estudios de asociación amplia del genoma muestra que ciertos perfiles genéticos aumentan el riesgo de enfermedad arterial coronaria (EAC) y de ataques cardíacos en quienes presentan el trastorno. Los resultados del estudio se publican en la edición digital de la revista The Lancet.

Los investigadores compararon a 12.393 individuos con EAC con 7.383 personas que no presentaban el trastorno para identificar localizaciones genéticas que predisponen a la enfermedad cardíaca. Para descubrir las localizaciones, compararon a 5.783 pacientes de EAC que habían tenido un ataque cardíaco con 3.644 individuos con la enfermedad, pero que no habían tenido infarto.

Los autores descubrieron una nueva localización, ADAMTS7, que aumentaba el riesgo de desarrollar EAC. En la comparación sobre ataques cardíacos, los resultados indicaron una nueva asociación en el grupo sanguíneo AB0. Descubrieron que el mismo gen que codifica la enzima en personas del grupo 0 proporcionaba protección contra los ataques cardíacos.

Según concluyen los investigadores, los descubrimientos indican que existen variantes genéticas específicas que predisponen al desarrollo de aterosclerosis coronaria, mientras que otras predisponen a la posterior ruptura de las placas y al ataque cardíaco agudo. "La relación con fenotipos específicos de la EAC podría modificar cómo se aplican las nuevas localizaciones a la evaluación de riesgos personalizados y al desarrollo de nuevas terapias para la EAC", afirman.


The Lancet (15 January 2011); doi:10.1016/S0140-6736(10)61996-4
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies : The Lancet

Universidad de Pensilvania
Penn: University of Pennsylvania

Actualidad Ultimas noticias - JANOes - Identifican variantes geneticas que predisponen a la aterosclerosis y al infarto de miocardio - JANO.es - ELSEVIER