الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Background: Signal transducer and activator of transcription 3 (STAT3), a potential genetic factor contributing to osteoarthritis (OA) pathogenesis, has been shown to be regulated by microRNAs (miRNAs). Therefore, it seems reasonable to hypothesize that polymorphisms in 3′ untranslated region (3′-UTR) of STAT3 mRNA can derange STAT3 gene expression via disrupting miRNA binding site. This study aimed to examine the impact of STAT3 rs1053005 variant and miR-452-3p expression on OA susceptibility.
Subjects and methods: 258 OA patients and 200 healthy controls were enrolled in the study. Inflammatory markers of disease activity were measured using enzyme-linked immunosorbent assay (ELISA) technique. STAT3 genotyping was carried out using allelic-discrimination PCR, while STAT3 and miR-452-3p expression analysis was conducted by quantitative real-time PCR.
Results: In OA patients, STAT3 expression was up-regulated and positively associated with plasmin, tumor necrosis factor alpha (TNF-α), matrix metalloproteinases-3 (MMP-3) and STAT3 serum levels, while miR-452-3p expression was down-regulated and negatively associated with the previously mentioned parameters’ levels. OA patients had a lower prevalence of the G minor allele of the STAT3 rs1053005 variant (p<0.001). Plasmin, TNF-α, MMP-3, and STAT3 mRNA and protein levels were significantly lower, while miR-452-3p expression was significantly higher in the GG genotype carriers compared to AG and AA genotypes carriers.
Conclusions: The minor G allele of STAT3 rs1053005 (A/G) polymorphism was associated with decreased OA susceptibility and severity; possibly via enhancing miR-452-3p binding to STAT3 mRNA target with subsequent diminished STAT3 expression.
Keywords: Osteoarthritis; STAT3; miR-452-3p; rs1053005.