Physiol Genomics. 2016 Nov 1;48(11):810-815. doi: 10.1152/physiolgenomics.00059.2016.

Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease.

Pereira A1, Palma Dos Reis R2, Rodrigues R3, Sousa AC3, Gomes S3, Borges S3, Ornelas I3, Freitas AI4, Guerra G4, Henriques E3, Rodrigues M3, Freitas S3, Freitas C3, Brehm A4, Pereira D3, Mendonça MI3.
1 Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal; dep.card@sesaram.pt.
2 Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal;
3 Funchal Hospital Center, Research Unit and Cardiology Department, Funchal, Madeira, Portugal.
4 Laboratory of Human Genetics, Madeira University, Campus da Penteada, Funchal, Madeira, Portugal.

Abstract

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. Copyright © 2016 the American Physiological Society.
KEYWORDS:ADAMTS7 gene; coronary artery disease; single nucleotide polymorphism (SNP), cardiovascular survival
PMID: 27614204
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