Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Titel eines Journals oder einer Zeitschrift: | Circulation | ||||
Verlag: | LIPPINCOTT WILLIAMS & WILKINS | ||||
Ort der Veröffentlichung: | PHILADELPHIA | ||||
Band: | 117 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 13 | ||||
Seitenbereich: | S. 1675-1684 | ||||
Datum: | 2008 | ||||
Institutionen: | Medizin > Lehrstuhl für Innere Medizin II | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | MYOCARDIAL-INFARCTION; HEART-DISEASE; RISK-FACTORS; GENE; HAPLOTYPES; GENOME; chromosomes; coronary disease; genetics; meta-analysis; myocardial infarction; risk factors | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 68229 |
Zusammenfassung
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 and Results - A single-nucleotide polymorphism (SNP), rs1333049, representing the 9p21.3 locus, was genotyped in 7 case-control ...
Zusammenfassung
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 and Results - 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 = 6.04 x 10(-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. Conclusion - This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.
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