Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease.
Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal; dep.card@sesaram.pt.
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Pereira
Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal; and.
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Palma Dos Reis
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Rodrigues
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Sousa
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Gomes
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Borges
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Ornelas
Laboratory of Human Genetics, Madeira University, Campus da Penteada, Funchal, Madeira, Portugal.
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Freitas
Laboratory of Human Genetics, Madeira University, Campus da Penteada, Funchal, Madeira, Portugal.
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Guerra
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Henriques
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Rodrigues
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Freitas
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Freitas
Laboratory of Human Genetics, Madeira University, Campus da Penteada, Funchal, Madeira, Portugal.
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Brehm
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Pereira
Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
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Mendonça
D000071118:ADAMTS7 Protein / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016019:Survival Analysis
D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human
ADAMTS7 gene; coronary artery disease; single nucleotide polymorphism (SNP), cardiovascular survival