MMP-2 gene polymorphisms are associated with type A aortic dissection and aortic diameters in patients

Abstract

Matrix metalloproteinases-2 (MMP-2) plays an important role in the pathogenesis of type A aortic dissection (AD). The aim of this study was to evaluate the association of 3 single nucleotide polymorphisms (SNPs) in the MMP-2 gene with type A AD risk and aortic diameters in patients. We performed a case–control study with 172 unrelated type A AD patients and 439 controls. Three SNPs rs11644561, rs11643630, and rs243865 were genotyped through the MassARRAY platform. Allelic associations of SNPs and SNP haplotypes with type A AD and aortic diameters in patients were evaluated. The frequency of the G allele of the rs11643630 polymorphism was significantly lower in type A AD patients than in control subjects (odds ratio 0.705, 95% confidence interval 0.545–0.912, P = 0.008). The association remained significant after adjusting for clinical covariates (P = 0.008). Carriers of the GG genotype of the rs11643630 polymorphism had significantly smaller aortic diameters than those with GT genotype or TT genotype (P = 0.02). Further haplotype analysis identified 1 protective haplotype (GC; P = 0.008) for development of type A AD. Again, a significant correlation was observed between haplotype GC and AD size (P = 0.020). Our results suggest that MMP-2 gene polymorphisms contribute to type A AD susceptibility. In addition, MMP-2 gene SNPs are associated with AD size, which could be used as a target for the development of new drug therapy.

Matrix metalloproteinase family polymorphisms and the risk of aortic aneurysmal diseases: A systematic review and meta‐analysis

“…MMP2rs11643630T/G is located in approximately 4 and 2.6 kb upstream of transcription initiation site and may be involved in the disease in a complex way. 26 Our results showed a strong correlation between the rs11643630 G allele and a deceased risk for TAD. In an individual study, Ruvolo et al found that…”

“…In our meta‐analysis, no obvious association of MMP2rs1053605 polymorphism with overall AA was detected. MMP2rs11643630T/G is located in approximately 4 and 2.6 kb upstream of transcription initiation site and may be involved in the disease in a complex way . Our results showed a strong correlation between the rs11643630 G allele and a deceased risk for TAD.…”

Cerebral small vessel disease and systemic arteriopathy in intracranial arterial dolichoectasia patients

“…The thoracoabdominal was the most frequently involved district. 30,31 In our patients, the presence of intimal thickening and plaques with or without stenoses likely reflects the coexistence of IADE and systemic atherosclerosis. However, the reported findings are not of univocal interpretation from a pathogenic point of view and need to be confirmed in larger patient series.…”

“…26 Likewise, a proteolytic imbalance induced by specific metalloproteinase polymorphisms has also been related to the development of thoracic aorta dissection and coronary artery ectasia. 30,31 In our patients, the presence of intimal thickening and plaques with or without stenoses likely reflects the coexistence of IADE and systemic atherosclerosis. In the past, due to the fact that IADE and atherosclerosis share similar risk factors, these disorders were pos- In the GENIC Study, the lack of any association between IADE and several ultrasonographic markers of atherosclerosis such as common carotid arteries intima-media thickness and carotid plaques corroborated on clinical grounds the hypothesis that IADE is not an ectatic variant of atherothrombotic disease.…”

Polymorphisms and pharmacogenomics for the toxicity of methotrexate monotherapy in patients with rheumatoid arthritis

“…[61,62] Several studies have shown that SNPs could explain differences in genetic susceptibility to different diseases. [63,64] In recent years, extensive pharmacogenomics investigations have been performed to optimize MTX therapy for RA patients through genotyping and/or gene-expression-based tests. These tests were primarily based on mRNA and included transporters, enzymes, and metabolites genes [57] ; however, the majority of the findings were inconclusive and inconsistent, even for classical candidate gene polymorphisms.…”