Genome-wide association scan identifies variants near Matrix Metalloproteinase (MMP) genes on chromosome 11q21-22 strongly associated with serum MMP-1 levels.
Circ Cardiovasc Genet
; 2(4): 329-37, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-20031604
ABSTRACT
BACKGROUND:
Matrix metalloproteinase (MMP)-1 may play a role in cardiovascular disease susceptibility by influencing plaque rupture via its ability to degrade extracellular collagens. METHODS ANDRESULTS:
We performed a genome-wide association analysis of circulating MMP-1 levels using 500 K single-nucleotide polymorphisms (SNPs) to identify genes influencing variation in serum MMP-1 levels in 778 healthy Amish adults. Serum MMP-1 levels, logarithm transformed, and adjusted for age and sex, were screened for association with SNPs using mixed-model variance components to account for familial relatedness. Median MMP-1 level was 3.05 ng/mL (interquartile range 1.82 to 5.04 ng/mL) with an estimated heritability of 81% (P<0.0001). Serum MMP-1 levels were strongly associated with a cluster of 179 SNPs extending over an 11.5-megabase region on chromosome 11q. The peak association was with rs495366 (P = 5.73 x 10(-34)), located within the region between MMP-1 and MMP-3 and having a minor allele frequency of 0.36. Two other SNPs within the 11q region, rs12289128 and rs11226373, were strongly associated with MMP-1 levels after accounting for rs495366 (P < or = 10(-7)). These 3 SNPs explained 31% of the variance in MMP-1 levels after adjusting for age and sex.CONCLUSIONS:
This study provides strong evidence that the serum MMP-1 level is highly heritable and that SNPs near MMPs on chromosome 11q explain a significant portion of the variation in MMP-1 levels. Identification of the genetic variants that influence MMP-1 levels may provide insights into genetic mechanisms of cardiovascular disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 11
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Metaloproteinasa 1 de la Matriz
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Metaloproteinasas de la Matriz
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Polimorfismo de Nucleótido Simple
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Circ Cardiovasc Genet
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
GENETICA MEDICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos