Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients

Alzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extra...

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Main Authors: Vladimira Durmanova, Juraj Javor, Zuzana Parnicka, Gabriel Minarik, Agata Ocenasova, Barbora Vaseckova, Veronika Reznakova, Maria Kralova, Tomas Hromadka, Ivana Shawkatova
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/5573642
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author Vladimira Durmanova
Juraj Javor
Zuzana Parnicka
Gabriel Minarik
Agata Ocenasova
Barbora Vaseckova
Veronika Reznakova
Maria Kralova
Tomas Hromadka
Ivana Shawkatova
author_facet Vladimira Durmanova
Juraj Javor
Zuzana Parnicka
Gabriel Minarik
Agata Ocenasova
Barbora Vaseckova
Veronika Reznakova
Maria Kralova
Tomas Hromadka
Ivana Shawkatova
author_sort Vladimira Durmanova
collection DOAJ
description Alzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44±6.28 vs. 76.36±6.39, p=0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61±5.88 vs. 78.57±6.79, p=0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.
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spelling doaj-art-205393bd007749a3bcaa62ae13a91a5c2025-02-03T06:07:16ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/55736425573642Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease PatientsVladimira Durmanova0Juraj Javor1Zuzana Parnicka2Gabriel Minarik3Agata Ocenasova4Barbora Vaseckova5Veronika Reznakova6Maria Kralova7Tomas Hromadka8Ivana Shawkatova9Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaDepartment of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaPsychiatry Outpatient Clinic, University Hospital and Polyclinic the Brothers of Saint John of God in Bratislava, SlovakiaCare Centre Centrum Memory, Bratislava, SlovakiaClinic of Psychiatry, Faculty of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaAlzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44±6.28 vs. 76.36±6.39, p=0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61±5.88 vs. 78.57±6.79, p=0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.http://dx.doi.org/10.1155/2021/5573642
spellingShingle Vladimira Durmanova
Juraj Javor
Zuzana Parnicka
Gabriel Minarik
Agata Ocenasova
Barbora Vaseckova
Veronika Reznakova
Maria Kralova
Tomas Hromadka
Ivana Shawkatova
Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients
Mediators of Inflammation
title Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients
title_full Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients
title_fullStr Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients
title_full_unstemmed Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients
title_short Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients
title_sort impact of mmp2 rs243865 and mmp3 rs3025058 polymorphisms on clinical findings in alzheimer s disease patients
url http://dx.doi.org/10.1155/2021/5573642
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