Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.
Circulation
; 117(13): 1675-84, 2008 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-18362232
ABSTRACT
BACKGROUND:
Recently, genome-wide association studies identified variants on chromosome 9p21.3 as affecting the risk of coronary artery disease (CAD). We investigated the association of this locus with CAD in 7 case-control studies and undertook a meta-analysis. METHODS ANDRESULTS:
A single-nucleotide polymorphism (SNP), rs1333049, representing the 9p21.3 locus, was genotyped in 7 case-control studies involving a total of 4645 patients with myocardial infarction or CAD and 5177 controls. The mode of inheritance was determined. In addition, in 5 of the 7 studies, we genotyped 3 additional SNPs to assess a risk-associated haplotype (ACAC). Finally, a meta-analysis of the present data and previously published samples was conducted. A limited fine mapping of the locus was performed. The risk allele (C) of the lead SNP, rs1333049, was uniformly associated with CAD in each study (P<0.05). In a pooled analysis, the odds ratio per copy of the risk allele was 1.29 (95% confidence interval, 1.22 to 1.37; P=0.0001). Haplotype analysis further suggested that this effect was not homogeneous across the haplotypic background (test for interaction, P=0.0079). An autosomal-additive mode of inheritance best explained the underlying association. The meta-analysis of the rs1333049 SNP in 12,004 cases and 28,949 controls increased the overall level of evidence for association with CAD to P=6.04x10(-10) (odds ratio, 1.24; 95% confidence interval, 1.20 to 1.29). Genotyping of 31 additional SNPs in the region identified several with a highly significant association with CAD, but none had predictive information beyond that of the rs1333049 SNP.CONCLUSIONS:
This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Variación Genética
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Cromosomas Humanos Par 9
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Enfermedad de la Arteria Coronaria
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Secuencias Repetitivas de Ácidos Nucleicos
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Polimorfismo de Nucleótido Simple
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Circulation
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania