6533b852fe1ef96bd12aac26
RESEARCH PRODUCT
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
Calogera PisanoAlberto AllegraBalistrericarmela RitaCandoregiuseppinaGiovanni RuvoloDomenico LioOreste Fabio TrioloVincenzo ArganoFloriana Crapanzanosubject
MalePathologyHeart Valve DiseasesDisease030204 cardiovascular system & hematologyMatrix metalloproteinasers3918242 rs243865 rs2285053 MMP-2 and MMP-9 gene SNPDegenerative 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; Heart Valve Diseases; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Mitral Valve; Prospective Studies; Risk Factors; Polymorphism Single Nucleotide0403 veterinary scienceCohort Studies0302 clinical mediciners2285053 MMP-2 and MMP-9 gene SNPsRisk FactorsGenotypeManagement and outcomeNatriuretic peptideProspective StudiesProspective cohort studyMVDSMetalloproteinaseDegenerative forms of mitral valve diseases04 agricultural and veterinary sciencesGeneral MedicineSingle NucleotideMiddle AgedMetalloproteinasesPathophysiologyMatrix Metalloproteinase 9Matrix Metalloproteinase 2Mitral ValveFemalers3918242Cardiology and Cardiovascular MedicineDegenerative forms of mitral valve diseasemedicine.medical_specialtyGenotype040301 veterinary sciencesmedicine.drug_class2734Single-nucleotide polymorphismDegenerative forms of mitral valve diseases; Management and outcome; Metalloproteinases; rs3918242 rs243865 rs2285053 MMP-2 and MMP-9 gene SNPs; Cardiology and Cardiovascular Medicine; 2734Polymorphism Single NucleotidePathology and Forensic Medicine03 medical and health sciencesInternal medicinemedicineHumansGenetic Predisposition to Diseasers243865PolymorphismAgedbusiness.industrySettore MED/23 - Chirurgia Cardiacabusinessdescription
Abstract 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 |