A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease.
Arterioscler Thromb Vasc Biol
; 27(9): 2030-6, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17569884
ABSTRACT
OBJECTIVES:
The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD). METHODS ANDRESULTS:
We used 3 case-control studies of white subjects whose severity of CAD was assessed by angiography. The first 2 studies were used to generate hypotheses that were then tested in the third study. We tested 12,077 putative functional single nucleotide polymorphisms (SNPs) in Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally associated with severe CAD. Testing these 302 SNPs in Study 2 (471 cases, 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, and ABCG2) were nominally associated with severe CAD and had the same risk alleles in both studies. We then tested these 5 SNPs in Study 3 (554 cases, 373 controls). We found 1 SNP that was associated with severe CAD LPA I4399M (rs3798220). LPA encodes apolipoprotein(a), a component of lipoprotein(a). I4399M is located in the protease-like domain of apolipoprotein(a). Compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (confidence interval 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (P=0.003).CONCLUSIONS:
The LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
/
Predisposição Genética para Doença
/
Polimorfismo de Nucleotídeo Único
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Apoproteína(a)
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Ano de publicação:
2007
Tipo de documento:
Article