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THE EXPRESSION OF GENES LOCATED ON 4TH CHROMOSOME IN ASSOCIATION WITH SHORT TELOMERE LENGTH IN PATIENTS WITH RHEUMATOID ARTHRITIS


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Abstract

Quantitative fluorescent in situ hybridization with subsequent analysis of metaphase chromosomes showed that distribution of telomere length on each arm of individual chromosomes is irregular under normal and pathological conditions. Patients with rheumatoid arthritis were characterized by significantly shorter telomere length on the 4p chromosome.To study the telomere position effect we selected genes located in different regions of the 4 chromosome, which encode proteins associated with regulatory and pathogenic processes. Analysis of gene expression (mRNA) by real-time PCR detected no significant differences between donors and patients groups.However, there was a tendency to increase CTBP1expression almost in 2-fold and to reducelevel of IRF2 gene expression in 2,5 fold in patients with rheumatoid arthritis.We suggested that enlargement of CTBP1 transcripts may be related to the weakening of repressiveproperties of telomeric heterochromatin, while the other epigenetic mechanisms are involved in changing of IRF2 gene expression. In patients with moderate activity of the disease the mRNA amount of TLR2 gene and IRF2 gene differed from those in normal individuals. A tendency to increase in CTBP1 expression was registered in patients with high activity of rheumatoid arthritis compared to donors’ values. Furthermore, the activity of rheumatoid arthritis was inversely correlated with the telomerelength in p-arm of chromosome10.This area contains genes associated with a predisposition to the disease and involved in differentiation and proliferation of T cells. Further investigation will fully reveal the signaling pathways, which are responsible for development of rheumatoid arthritis, and establish new targets for the treatment of the disease.


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