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

Risultato della ricerca: Article

5 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)362-370
Numero di pagine9
RivistaCardiovascular Pathology
Volume25
Stato di pubblicazionePublished - 2016

Fingerprint

Matrix Metalloproteinases
Mitral Valve
Cohort Studies
Prospective Studies
Single Nucleotide Polymorphism
Genotype
Atrial Natriuretic Factor
Control Groups
Metalloproteases
Enzymes
Genes
Biomarkers
Pathology

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

Cita questo

@article{d793a717bfde4e0e804d0c763c011cae,
title = "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",
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.",
keywords = "Degenerative forms of mitral valve diseases; Management and outcome; Metalloproteinases; rs3918242, rs243865, rs2285053 MMP-2 and MMP-9 gene SNPs; Cardiology and Cardiovascular Medicine; 2734",
author = "Giuseppina Candore and Domenico Lio and Giovanni Ruvolo and Triolo, {Oreste Fabio} and Calogera Pisano and Balistreri, {Carmela Rita} and Vincenzo Argano and Floriana Crapanzano and Giovanni Ruvolo",
year = "2016",
language = "English",
volume = "25",
pages = "362--370",
journal = "Cardiovascular Pathology",
issn = "1054-8807",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - 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

AU - Candore, Giuseppina

AU - Lio, Domenico

AU - Ruvolo, Giovanni

AU - Triolo, Oreste Fabio

AU - Pisano, Calogera

AU - Balistreri, Carmela Rita

AU - Argano, Vincenzo

AU - Crapanzano, Floriana

AU - Ruvolo, Giovanni

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Degenerative forms of mitral valve diseases; Management and outcome; Metalloproteinases; rs3918242, rs243865, rs2285053 MMP-2 and MMP-9 gene SNPs; Cardiology and Cardiovascular Medicine; 2734

UR - http://hdl.handle.net/10447/180094

UR - http://www.elsevier.com/locate/carpath

M3 - Article

VL - 25

SP - 362

EP - 370

JO - Cardiovascular Pathology

JF - Cardiovascular Pathology

SN - 1054-8807

ER -