Influence of -174G/C IL-6 gene polymorphism on the susceptibility to rheumatoid arthritis in children and adults in the Republic Of Belarus

The usage of clinical and instrumental methods only may be not sufficient for early diagnosis of autoimmune rheumatic diseases, as well as for their course prediction. The progress of modern rheumatology is largely conditioned by the investigation of molecular-genetic nature of diseases and the identification of biomarkers that can significantly improve diagnostics and therapeutic approach. The present study aimed to evaluate the effect of -174G/C IL-6 gene polymorphism on the risk of developing rheumatoid arthritis (RA) in children and adults in Republic of Belarus. It was established that the CC genotype frequency (p = 0.01, OR = 2.19; 95 % CI [1.31-3.67]) as well as the С allele frequency (p = 0.03; OR = 1.44; 95 % CI [1.04-2.00]) was significantly higher among patients with juvenile idiopathic arthritis (JIA) in the entire group and especially in girls (p = 0.04, OR = 2.55; 95 % CI [1.22-5.36]) in comparison with the controls. In addition, there is a tendency to higher frequency of the С allele in adult patients with RA (p = 0.07), reaching statistical significance in the case of RF-negative arthritis (p = 0.03, OR = 3.04; 95 % CI [1.15-8.06]). The minor С allele (p = 0.03, OR = 2.04; 95 % CI [1.09-3.82]) and homozygous CC genotype (p = 0.02, OR = 3.34; 95 % CI [1.38-8.07]) are also associated with seronegative polyarthritis in children. Thus, the presence of this allele in the tested locus increases the likelihood of developing certain rheumatoid arthritis subtypes in adults and children and can be used to reveal individuals with genetic predisposition.

1. Nasonov E. L., Nasonova V. A. Rheumatology: The National Guidelines. Moscow, GEOTAR-Media, 2008. 720 p. (in Russian).

2. Hirano T., Matsuda T., Turner M., Miyasaka N., Buchan G., Tang B., Sato K., Shimi M., Maid R., Feldmann M., Kishi-moto T. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. European Journal of Immunology, 1988, vol. 18, no. 11, pp. 1797-1801. https://doi.org/10.1002/eji.1830181122

3. Dasgupta B., Corkill M., Kirkham B., Gibson T., Panayi G. Serial estimation of interleukin 6 as a measure of systemic disease in rheumatoid arthritis. The Journal of Rheumatology, 1992, vol. 19, no. 1, pp. 22-25.

4. Cronstein B. N. Interleukin-6: A Key Mediator of Systemic and Local Symptoms in Rheumatoid Arthritis. Bulletin of the NYU Hospital for Joint Diseases, 2007, vol. 65, suppl. 1, pp. S11-15.

5. Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J. S., Humphries S., Woo P. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. Journal of Clinical Investigation, 1998, vol. 102, no. 7, pp. 1369-1376. https://doi.org/10.1r72/jci2629

6. Wielinska J., Dratwa M., Swierkot J., Korman L., Iwaszko M., Wysoczanska B., Bogunia-Kubik K. IL-6 gene polymorphism is associated with protein serum level and disease activity in Polish patients with rheumatoid arthritis. HLA, 2018, July. https://doi.org/10.1111/tan.13355

7. Kiszel P., Mako V., Prohaszka Z., Cervenak L. Interleukin-6-174 promoter polymorphism does not influence IL-6 production after LPS and IL-1 beta stimulation in human umbilical cord vein endothelial cells. Cytokine, 2007, vol. 40. no. 1, pp. 17-22. https://doi.org/10.1016/j.cyto.2007.08.001

8. Smith A. J. P., Humphries S. E. Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine & Growth Factor Reviews, 2009, vol. 20, no. 1, pp. 43-59. https://doi.org/10.1016/j.cytogfr.2008.11.006

9. Dar S. A., Haque S., Mandal R. K., Sing T., Wahid M., Jawed A., Panda A. K., Akhter N., Lohani M., Areeshi M. Y., Rai G., Datt S., Bhattacharya S. N., Ramachandran V. G., Das S. Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis. Autoimmunity, 2017, vol. 50, no. 3, pp. 158-169. https://doi.org/10.1080/08916934.2016.1261833

10. Paine S. K., Sen A., Choudhuri S., Mondal L. K., Chowdhury I. H., Basu A., Mukherjee A., Bhattacharya B. Association of Tumor Necrosis Factor a, Interleukin 6, and Interleukin 10 promoter polymorphism with proliferative diabetic retinopathy in type 2 diabetic subjects. Retina, 2012, vol. 32, no. 6, pp. 1197-1203. https://doi.org/10.1097/iae.0b013e31822f55f3

11. Amr K., El-Awady R., Raslan H. Assessment of the -174G/C (rs1800795) and -572G/C (rs1800796) Interleukin 6 Gene Polymorphisms in Egyptian Patients with Rheumatoid Arthritis. Macedonian Journal of Medical Sciences, 2016, vol. 4, no. 4, pp. 574-577. https://doi.org/10.3889/oamjms.2016.110