RELATION OF MMPS PROMOTER POLYMORPHISMS TO FACTORS DESCRIBING RHEUMATOID ARTHRITIS

Authors

PÁVKOVÁ GOLDBERGOVÁ Monika LIPKOVÁ Jolana PÁVEK Nikolas NĚMEC Petr GATTEROVA Jindra SOUČEK Miroslav VAŠKŮ Anna

Year of publication 2013
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Matrix metalloproteinases (MMPs) as a family of zinc-dependent endopeptidases have been involved in remodelling the extracellular matrix (ECM) not only in rheumatoid arthritis (RA). The promoter polymorphism variants in the MMPs genes can contribute to the onset, progression and severity of RA due to influence of promoter activity leading to altered expression. Objectives: The aim of the study was to examine the relation among polymorphisms and serum levels of selected MMPs (MMP-2, MMP-3, MMP-7, MMP-12, MMP-13), production of auto-antibodies, and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp score. Methods: A total of 156 RA patients according to the ACR criteria, and 100 control subjects were recruited into the study. The measurements of CRP, anti-CCP, presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp score (TSS), DAS28 and MMPs (MMP-3, MMP-13) levels in serum were obtained from all RA patients. Results: Complete or almost complete linkage disequilibrium was observed for MMP-2 polymorphisms (-790T/G, -1575A/G, -1306C/T; p < 0.001). All these MMP-2 promoter polymorphisms were related to RF IgG levels (p < 0.05) and RF IgG positivity/negativity (p < 0.01), IL-15 levels (p < 0.05), and in a trend to TNF alpha levels. Higher prevalence of T allele (-790T/G), C allele (-1306C/T) and G allele (-1575A/G) in the RF IgG positive subgroup was observed. The -135G/C MMP-7 polymorphism was related to activity of the disease; the variation was associated to DAS28 score (p < 0.01), TTS (p = 0.05) and HAQ (p = 0.03). A trend of relation between -77G/A MMP-13 polymorphism and TNF alpha levels was found (p = 0.06). No relation of promoter polymorphisms -11715A/6A MMP-3 and -77G/A MMP-13 to MMPs serum levels was proved. The MMP-3 serum level correlated to IL-6 (p = 0.02) and CRP (p = 0.05) levels. Conclusion: In conclusion, we present an association of MMPs gene polymorphisms with the rheumatoid factor IgG, and disease activity.

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