title: Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1β as a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients.
abstract: The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2G MMP1, -1562 C/T MMP9, -82 A/G MMP12, -511 C/T IL-1β, and 372 T/C TIMP1 genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA. In vivo promoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression of MMP1, MMP9, MMP12, and IL-1β genes as compared to the control group (P < 0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1β compared to the control group (P < 0.001). Allele -1607 1G of MMP1 gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C of MMP9 gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Markiewicz
authors.affiliation: Department of Cancer Biology, AFCRI, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA ; Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Pytel
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Mucha
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, 03-709 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szymanek
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, 03-709 Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, 03-709 Warsaw, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-647 Lodz, Poland.
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Majsterek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009898:Optic Disk / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1