Investigation of the Asp299Gly and Thr399Ile polymorphisms of TLR4 gene in Rheumatoid Arthritis

Year 2019, Volume: 46 Issue: 2, 255 - 268, 11.06.2019

İbrahim Halil Yildirim Ramazan Uzen

https://doi.org/10.5798/dicletip.540004

Abstract

Objective:
Rheumatoid arthritis (RA) is a chronic and inflammatory disease characterized
by synovial inflammation that causes cartilage and bone destruction as well as
systemic defects, including cardiovascular, pulmonary, psychological, and
skeletal disorders. The etiology of RA is unclear. Evidence suggests that RA is
influenced by both genetic and environmental factors and the inflammatory and
autoimmune activities take important roles in the development of this disease.
In the onset of RA, an interaction between the resident cells of synovium and
cells of the innate and adaptive immune system reported. Fibroblast-like
synoviocytes (FLS) are one of the resident cells and they play a central role,
with a tumor-like behavior, in joint destruction and development of chronic
inflammation. Toll-like receptors (TLRs) are transmembrane glycoproteins that
are related to inflammation via synthesis of proinflammatory cytokines like
TNF-α, IL-6, and IL-1β. Some studies report an association between the
activation of FLS and the cytokine environment, cell-to-cell contacts, or the
activation of TLR2, TLR4, and TLR3. TLRs and especially TLR4 is involved in the
recognition of endogenous molecules released by injured tissues and necrotic
cells. TLR4 gene involved in a wide variety of both infectious and
non-infectious diseases and two polymorphisms of TLR4, Asp299Gly and Thr399Ile,
changed the binding capacity and electrical charge of the protein. There are
conflicting or even contradictory results about these polymorphisms and we aimed
to determine the distribution of the allele frequencies of these polymorphisms
and compare the result of RA patients with healthy subjects.

Methods:
DNA extraction was realized by salting out method from peripheral blood
lymphocytes of RA patients and healthy controls. PCR amplification carried out
with appropriate primer pairs against the related DNA sequences. Genotyping
performed by the restriction fragment length polymorphism method.

Results and
Conclusion: According to the results obtained from RA patients and healthy
controls, we have not found any statistical difference between both groups.
Including the other polymorphisms of the TLR family into this type of studies,
will give more information about the role of TLR family in rheumatoid arthritis.

Keywords

Rheumatoid Arthritis, Toll-like receptor 4, polymorphism

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