ASSOCIATION BETWEEN MICRORNA 196A-2 POLYMORPHISM AND SERUM TYROSINASE LEVEL AND ITS INFLUENCE ON TREATMENT OF VITILIGO PATIENTS

Riham A. Abd Elsamie*, Khaled M. Hussein, Ihab Y. Abd Allah, Hanan S. Hassan, Asmaa A. Elfalah

ABSTRACT

Background: MicroRNAs (miRNAs) are discovered family of endogenous, noncoding RNA molecules. miRNAs modulate the gene expression post-transcriptionally by binding to complementary sequences in the coding or 3' untranslated region of target mRNAs. It was demonstrated also that miRNAs are the key regulators of a variety of biological processes such as cell proliferation, apoptosis and tumorigenesis. The miR-196a-2 could also potentially target genes such as platelet-derived growth factor receptor, alpha-polypeptide (PDGFRα), IL2, and mannose-binding lectin (protein C) 2 (MBL2) that are likely candidates of several oxidative stress-mediated diseases. In addition, miR-196a-2 was also demonstrated to target tyrosinase, which plays an important role in melanin synthesis. The aim of this study was to investigate the association between a functional SNP of rs 11614913 in microRNA 196a-2 and the serum tyrosinase level in vitiligo patients, evaluate the effect of microRNA 196a-2 polymorphism on the response to treatment in vitiligo patients, as well as to explore this polymorphism in first degree relatives of vitiligo patients. Methods: The current study was a prospective case-control interventional study that was conducted on 100 participants. Fifty of them were patients with vitiligo, and they were located in group 1. Group 2 contained 50 control participants, half of them were 1st-degree relatives for vitiligo patients (group 2a), while the rest had a negative family history. In group 1, determination of the miRNA 196a-2 polymorphism as well as assay of the level of serum Tyrosinase. Then, they were treated for 4 months by NB-UVB. Then after the end of the treatment course, serum tyrosinase level was remeasured and the response of the treatment was evaluated. Group 2 was tested also for the type of polymorphism and the level of serum Tyrosinase. Results: The level of serum tyrosinase is higher in patients with vitiligo. And the levels of the enzyme were significantly higher in cases suffering from early onset vitiligo. Patients with higher serum Tyrosinase level tended to be more resistant to treatment. And the treatment course of vitiligo failed to record a significant reduction in the serum Tyrosinase levels. T allele of miRNA 196a-2 polymorphism was found to have a significant relation with the development of vitiligo. And presence of TT genotype could predict the early age of onset and poor response to treatment, while C allele is associated with lower level of serum Tyrosinase level. Conclusion: MiRNA 196a-2 polymorphism could be used as a predictive marker for the expected development of vitiligo.

Keywords: Vitiligo; tyrosinase; polymorphism; microRNA.