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AB0099 Relation of mmps promoter polymorphisms to factors describing rheumatoid arthritis
  1. M. Pavkova Goldbergova1,
  2. J. Lipkova1,
  3. N. Pavek1,
  4. P. Nemec2,
  5. J. Gatterova3,
  6. J. Sevcikova1,
  7. M. Soucek2,
  8. A. Vasku1
  1. 1Institute of Pathological Physiology, Masaryk Univerity
  2. 22nd. Dept. of Internal Medicine, St. Anne’s Faculty Hospital Brno and Faculty of Medicine Masaryk University, Brno
  3. 3Institute of Rheumatology, Prague, Czech Republic

Abstract

Background 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.

Conclusions In conclusion, we present an association of MMPs gene polymorphisms with the rheumatoid factor IgG, and disease activity.

Disclosure of Interest None Declared

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