Role of Polymorphisms in Mmp-9 and Timp-1 As Biomarkers for Susceptibility to Systemic Lupus Erythematosus Patients

Abstract

Aim: To investigate the possible association between MMP-9 (-1562 C/T) and TIMP-1 (372 T/C) polymorphism and inflammatory markers with disease activity in systemic lupus erythematosus (SLE) patients. Materials & methods: 150 SLE patients were recruited. Disease severity was assessed by SLEDAI (SLE disease activity index). The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum levels by ELISA. Results: Among patients mean MMP-9 serum levels and mRNA expression were significantly decreased with increase in TIMP-1 levels (p < 0.0001). Concomitant presence of both MMP-9 1562 T and TIMP-1 372 C alleles synergistically increased risk of SLE by 7.89-fold (p < 0.0001). The mRNA expression of MMP-9 and TIMP-1 correlated with SLEDAI score. Conclusion: MMP-9, TIMP-1 and MMP-9/TIMP-1 ratios may act as biomarkers for susceptibility to SLE.

Keywords:

• autoantibodies
• biomarker
• disease activity
• India
• inflammatory markers
• MMP-9
• mRNA expression
• polymorphism
• SLE
• TIMP-1

Author's contribution

All authors have contributed sufficiently to the project to be included as authors. H Vira and V Umare performed the research and wrote the manuscript. A Nadkarni and V Pradhan designed the research study and helped in writing the manuscript. A Rajadhyksha and M Nadkar did clinical evaluation of the patients. A Chaudhary and K Ghosh contributed in data analysis.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors thank the Indian Council of Medical Research (ICMR), New Delhi, India and University of Mumbai for their support.