title: Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus: correlation with systemic inflammatory markers and oxidative stress.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs and is characterized by persistent systemic inflammation. Among the effects of inflammatory mediators, the induction of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and oxidative stress has been demonstrated to be important in the development of SLE. In this study, the possible association between MMP-9 and MMP-2 functional promoter polymorphism, stress, and inflammatory markers with development of severe cardiovascular disease (CVD), high blood pressure (HBP), and lupus nephropathy (LN) in SLE patients was investigated. The present case-control study consisted of 109 SLE patients with and without CVD, HBP and LN and 101 gender- and age-matched unrelated healthy controls from a population in western Iran. MMP-2 -G1575A and MMP-9 -C1562T polymorphisms were detected by PCR-RFLP, serum MMP-2 and MMP-9, neopterin, malondialdehyde (MDA) and lipid levels were determined by ELISA, HPLC and enzyme assay, respectively. We found that MMP-9 -C1562 T and MMP-2 -G1575A alleles act synergistically to increase the risk of SLE by 2.98 times (p = 0.015). Findings of this study also demonstrated that there is a significant increase in the serum levels of MMP-2, neopterin and MDA and a significant decrease in serum level of MMP-9 in the presence of MMP-9-C1562 T and MMP-2 -G1575A alleles in SLE patients compared to controls. Further, SLE patients with MMP-9 (C/T + T/T) genotype had significantly higher serum concentrations of MMP-2, neopterin, MDA and LDL-C, but lower serum MMP-9 and HDL-C levels than corresponding members of the control group. MMP-9 (C/T + T/T) genotype increased risk of hypertension in SLE patients 2.71-fold. This study for the first time not only suggests that MMP-9 -C1562 T and MMP-2 -G1575A alleles synergistically increase the risk of SLE but also high serum levels of MDA, neopterin, and circulatory levels of MMP-2 and lower MMP-9 in SLE patients. This information may be important in the evaluation of SLE progression and in the elucidation of the mechanisms of the disease pathogenesis.
authors.affiliation: Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Bahrehmand
authors.affiliation: Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran asadvaisiraygani@kums.ac.ir avaisiraygani@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.affiliation: Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Department of Toxicology and Pharmacology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Kiani
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Z
authors.initials: Z
authors.lastname: Rahimi
authors.affiliation: Department of Clinical Biochemistry, Hamedan University of Medical Sciences, Kermanshah, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Tavilani
authors.affiliation: Kidney Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Ardalan
authors.affiliation: Department of Chemistry, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Vaisi-Raygani
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: E
authors.initials: E
authors.lastname: Shakiba
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee, Health Science Center, USA tpourmotabbe@utmem.edu tpourmotabbe@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Pourmotabbed
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000201:enzymology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide
chemical_list: D015415:Biomarkers; D008315:Malondialdehyde; D019798:Neopterin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Systemic lupus erythematosus; malondialdehyde; matrix metalloproteinase-2 –C1562T functional promoter; matrix metalloproteinase-9 –C1562T functional promoter; neopterin