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.
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.


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.


CONCLUSIONS
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.
Department of Pathobiology and Medical Biotechnologies, University of Palermo, Italy.
Carmela Rita
CR
Balistreri
Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, Italy.
Alberto
A
Allegra
Department of Pathobiology and Medical Biotechnologies, University of Palermo, Italy.
Floriana
F
Crapanzano
Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, Italy.
Calogera
C
Pisano
Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, Italy.
Oreste Fabio
OF
Triolo
Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, Italy.
Vincenzo
V
Argano
Department of Pathobiology and Medical Biotechnologies, University of Palermo, Italy.
Giuseppina
G
Candore
Department of Pathobiology and Medical Biotechnologies, University of Palermo, Italy.
Domenico
D
Lio
Department of Cardiac Surgery, University of Rome 'Tor Vergata', Italy.
Giovanni
G
Ruvolo
D000368:Aged; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006349:Heart Valve Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D008943:Mitral Valve / Q000473:pathology* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Degenerative forms of mitral valve diseases; Management and outcome; Metalloproteinases; rs3918242, rs243865, rs2285053 MMP-2 and MMP-9 gene SNPs