Associations of rs3918242 and rs2285053 MMP-9 and MMP-2 polymorphisms with the risk, severity, and short- and long-term complications of degenerative mitral valve diseases: A 4.8-year prospective cohort study
| Autor: | Calogera Pisano, Alberto Allegra, Carmela Rita Balistreri, Giuseppina Candore, Giovanni Ruvolo, Domenico Lio, Oreste Fabio Triolo, Vincenzo Argano, Floriana Crapanzano |
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| Přispěvatelé: | Balistreri, C., Allegra, A., Crapanzano, F., Pisano, C., Triolo, O., Argano, V., Candore, G., Lio, D., Ruvolo, G. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Pathology Heart Valve Diseases Disease 030204 cardiovascular system & hematology Matrix metalloproteinase rs3918242 rs243865 rs2285053 MMP-2 and MMP-9 gene SNP Degenerative forms of mitral valve diseases Management and outcome Metalloproteinases rs3918242 rs243865 rs2285053 MMP-2 and MMP-9 gene SNPs Aged Cohort Studies Female Genetic Predisposition to Disease Genotype Humans Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Middle Aged Mitral Valve Prospective Studies Risk Factors Polymorphism Single Nucleotide 0403 veterinary science 0302 clinical medicine rs2285053 MMP-2 and MMP-9 gene SNPs Natriuretic peptide Prospective cohort study MVDS Metalloproteinase 04 agricultural and veterinary sciences General Medicine Single Nucleotide Pathophysiology rs3918242 Cardiology and Cardiovascular Medicine Degenerative forms of mitral valve disease medicine.medical_specialty 040301 veterinary sciences medicine.drug_class Single-nucleotide polymorphism 2734 Pathology and Forensic Medicine 03 medical and health sciences Internal medicine medicine rs243865 Polymorphism business.industry Settore MED/23 - Chirurgia Cardiaca business |
| Popis: | Background Degenerative forms of mitral valve diseases (MVDs) are very complex pathologies. Thus, it is difficult to make generalizations about the disease pathways or genetic risk factors contributing to these diseases. However, a key role of metalloproteinases (MMPs) in their pathophysiology is emerging. Thus, we performed for the first time a perspective study to assess eventual associations of some functional single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes with the MVD risk, symptom severity, and short- and long-term (4.8 years) complications. Materials and methods For this purpose, 90 patients and two control groups were genotyped for rs3918242, rs243865, and rs2285053 MMP-2 and MMP-9 gene SNPs, and systemic levels of pro-atrial natriuretic peptide (pro-ANP) and two enzymes were quantified and correlated to genotypes of MMP-2 and MMP-9 SNPs studied. In addition, associations between these SNPs and symptom severity and short- and long-term (4.8 years) complications were evaluated. Results Interestingly, rs3918242 MMP-9 and rs2285053 MMP-2 SNPs were significantly represented in cases than two control groups and were associated with a higher MVD risk, as demonstrated using dominant/recessive models. Cases stratified for NYHA symptoms and particularly those NYHA III+IV with rs3918242 CT+TT MMP-9 and rs2285053CT+TT genotypes also showed higher severity related to significant higher systemic levels of MMP enzymes and pro-ANP at enrolment and 4.8 follow-up times. In addition, cases with these genotypes and particularly those NYHA III+IV had a very significant percentage of complications, particularly at the 4.8 follow-up. Surprisingly, 20% of patient controls developed MVD at 4.8-year follow-up and were carriers of these genotypes. Conclusion Thus, the associations observed seem to suggest that the two SNPs might represent useful biomarkers and targets for preventing and monitoring MVDs and developing personalized treatments, consenting a more appropriate management and outcome. |
| Databáze: | OpenAIRE |
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