الفهرس 
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Abstract
SRheumatoid arthritis (RA) is a joint destructive disorder. This study aimed to assess the relation of long non-coding RNAs (lncRNAs) maternally expressed gene 3 (MEG3) and long intergenic non-protein coding RNA (LINC00305) expression and their genetic variants rs941576 and rs2850711, respectively with RA incidence, and activity in Egyptian patients.
Subjects and Methods: 100 RA patients and 100 healthy individuals were enrolled in the study. Quantitative PCR was used for expression analysis. Genotyping was by allelic discrimination technology.
Results: MEG3 was down-regulated in RA patients and negatively associated with RA clinical features, including Disease Activity Score in 28 joints (DAS-28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody and nuclear factor- kappa beta (NF-κB), hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-3 (MMP-3) and vascular endothelial growth factor (VEGF). On the contrary, it was positively associated with Bcl-2–associated X (Bax) serum levels in RA patients. The major A allele of rs941576 variant was more frequent in RA patients (p=0.0003). AA genotype carriers showed a significant decrease in MEG3 expression and Bax level and increase in HIF-1α and VEGF levels. Median LINC00305 expression level in RA patients was 7.29-fold higher than controls (p<0.001), and was positively correlated with RA disease activity indices and NF-κB, HIF-1α, MMP-3 and VEGF serum levels. On the other hand, it was negatively associated with Bax serum levels in RA patients. Individuals carrying AT and TT genotypes of rs2850711 polymorphism had significantly increased risk for RA than those carrying AA genotype (p<0.05). LINC00305 relative expression, DAS-28 score and serum levels of NF-κB and MMP-3 were significantly increased in the patients carrying LINC00305 AT and TT genotypes as compared with patients with the AA genotype (p<0.01).
Conclusions: Serum MEG3 expression showed negative association with increased susceptibility to RA. MEG3 gene rs941576 (A/G) polymorphism was associated with increased activity of RA in the current population. In addition, the expression level of LINC00305 and its rs2850711 genetic variant may play a role in RA susceptibility.