Polymorphisms of THBS1, GTF2I, STAT4, PTPN22 genes contributes to development of dry keratoconjunctivitis in patients with rheumatoid arthritis and primary Sjogren’s syndrome

  • T. N. Safonova Institute of Eye Diseases, Moscow, Russia
  • G. V. Zaitseva Institute of Eye Diseases, Moscow, Russia http://orcid.org/0000-0001-8575-3076
  • Z. V. Surnina Institute of Eye Diseases, Moscow, Russia
  • S. S. Lukina Institute of General Pathology and Pathophysiology, Moscow, Russia
  • V. I. Loginov Institute of General Pathology and Pathophysiology, Moscow, Russia http://orcid.org/0000-0003-2668-8096
  • A. M. Burdennyy Institute of General Pathology and Pathophysiology, Moscow, Russia; N.M. Emanuel Institute for Biochemical Physics, Moscow, Russia http://orcid.org/0000-0002-9398-8075
DOI: https://doi.org/10.25557/2310-0435.2020.02.71-78
Keywords: dry keratoconjunctivitis, primary Sjogren’s syndrome, rheumatoid arthritis, THBS1, GTF2I, STAT4, PTPN22 genes

Abstract

Background. Dry keratoconjunctivitis is a multifactorial disease of the ocular surface with a high prevalence among ophthalmic patients. This disease is associated with systemic autoimmune disorders (SID) and is characterized by the most severe clinical course. Rheumatoid arthritis (RA) and primary Sjogren’s syndrome (PSS) are the most common diagnoses among these diseases. Studies have shown a connection between PSS and RA with genetic factors. However presently, information about genes that play a role in the pathogenesis of these diseases remains incomplete.
Aim. The aim of this study was to determine the relationship of clinical and morphological findings with molecular genetic changes associated with dry keratoconjunctivitis in rheumatoid arthritis and Sjogren’s syndrome.
Methods. The study included 154 patients with RA and PSS (79 and 75, respectively). The control group consisted of 100 healthy volunteers without SID or family history. Changes in the studied genes were searched for and analysed with the melting curve analysis.
Results. We have identified an association between the degree of conjunctival epitheliopathy and the carriage of the G allele in the MUC1 gene rs4072037 marker. Also, the polymorphic marker rs1478604 of the THBS1 gene was shown to be associated with the risk of PSS (p = 0.001). The GG genotype of the rs1478604 marker was associated with severity of dry keratoconjunctivitis (p = 0.02) and with changes in the pathway and structure of corneal nerve fibres. At the same time, the GG genotype of the rs2228262 marker was associated only with severity of dry keratoconjunctivitis (p = 0.03). These data were obtained for the first time.
Conclusion. Development and implementation of methods for analysis of polymorphic variants of the genes used for diagnosing dry keratoconjunctivitis in rheumatoid arthritis and Sjögren’s primary syndrome will help detecting possible development of dry keratoconjunctivitis and/or its progression in patients with autoimmune diseases or people at risk.

Published
2020-06-19
How to Cite
Safonova, T. N., Zaitseva, G. V., Surnina, Z. V., Lukina, S. S., Loginov, V. I., & Burdennyy, A. M. (2020). Polymorphisms of THBS1, GTF2I, STAT4, PTPN22 genes contributes to development of dry keratoconjunctivitis in patients with rheumatoid arthritis and primary Sjogren’s syndrome. Patogenez (Pathogenesis), 18(2), 71-78. https://doi.org/10.25557/2310-0435.2020.02.71-78
Issue
Vol. 18 No. 2 (2020): Pathogenesis
Section
New technologies