Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus

Correlation with systemic inflammatory markers and oxidative stress

F. Bahrehmand, Asad Vaisi-Raygani, A. Kiani, Z. Rahimi, H. Tavilani, M. Ardalan, H. Vaisi-Raygani, E. Shakiba, Tayebeh Pourmotabbed

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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.

Original languageEnglish (US)
Pages (from-to)597-605
Number of pages9
JournalLupus
Volume24
Issue number6
DOIs
StatePublished - May 21 2015

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Matrix Metalloproteinase 9
Matrix Metalloproteinases
Systemic Lupus Erythematosus
Oxidative Stress
Neopterin
Malondialdehyde
Serum
Alleles
Hypertension
Cardiovascular Diseases
Genotype

All Science Journal Classification (ASJC) codes

  • Rheumatology

Cite this

Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus : Correlation with systemic inflammatory markers and oxidative stress. / Bahrehmand, F.; Vaisi-Raygani, Asad; Kiani, A.; Rahimi, Z.; Tavilani, H.; Ardalan, M.; Vaisi-Raygani, H.; Shakiba, E.; Pourmotabbed, Tayebeh.

In: Lupus, Vol. 24, No. 6, 21.05.2015, p. 597-605.

Research output: Contribution to journalArticle

Bahrehmand, F, Vaisi-Raygani, A, Kiani, A, Rahimi, Z, Tavilani, H, Ardalan, M, Vaisi-Raygani, H, Shakiba, E & Pourmotabbed, T 2015, 'Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus: Correlation with systemic inflammatory markers and oxidative stress', Lupus, vol. 24, no. 6, pp. 597-605. https://doi.org/10.1177/0961203314559085
Bahrehmand, F. ; Vaisi-Raygani, Asad ; Kiani, A. ; Rahimi, Z. ; Tavilani, H. ; Ardalan, M. ; Vaisi-Raygani, H. ; Shakiba, E. ; Pourmotabbed, Tayebeh. / Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus : Correlation with systemic inflammatory markers and oxidative stress. In: Lupus. 2015 ; Vol. 24, No. 6. pp. 597-605.
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AU - Shakiba, E.

AU - Pourmotabbed, Tayebeh

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N2 - 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.

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