Lack of significant association between selected STAT3 polymorphisms and rheumatoid arthritis in the Polish population
More details
Hide details
Submission date: 2018-03-26
Final revision date: 2018-04-14
Acceptance date: 2018-04-16
Online publication date: 2018-05-09
Publication date: 2018-04-30
Reumatologia 2018;56(2):73-79
Rheumatoid arthritis (RA) is the most common systemic inflammatory disease and is of unknown etiology. The altered balance between immunosuppressive and inflammatory T cell subpopulations exerts a huge impact on RA pathogenesis. The STAT3 protein regulates genes involved in the immune responses. It regulates maturation of T and B cells. Its abnormal activity is significantly associated with autoimmune diseases and cancer development. We aimed to evaluate the contribution of three potentially functional single nucleotide polymorphisms (SNPs) within the STAT3 gene to susceptibility and severity of RA in the Polish population.

Material and methods:
A total of 595 patients with RA and 330 healthy individuals were included in the study. DNA from patients and healthy subjects was obtained from peripheral blood using standard DNA isolating methods. The STAT3 rs1053005, rs1026916 and rs2293152 polymorphisms were genotyped using the TaqMan SNP genotyping assay. The accuracy of SNP genotyping was confirmed using direct DNA sequence analysis.

The distribution of STAT3 polymorphisms did not differ significantly between cases and controls. Our results revealed a tendency only, where rs1026916 AA genotype occurred more frequently in RA patients compared to healthy controls, in codominant (p = 0.09), dominant (p = 0.06) and recessive (p = 0.09) models. STAT3 rs2293152 polymorphism was associated with higher DAS28 (p = 0.014 codominant model; p = 0.003 dominant model), increased number of swollen joints (p = 0.02), higher VAS (p = 0.01) and higher HAQ score (p = 0.05).

We did not observe a significant association between the three studied STAT3 genetic variants and increased susceptibility to or severity of RA. Only the STAT3 rs2293152 polymorphism was associated with parameters that indicate a more severe course of the disease. However, its distribution did not differ between RA and control groups. According to our observations these 3 studied STAT3 SNPs may not be used as risk factors for developing RA.

Khurana R, Berney SM. Clinical aspects of rheumatoid arthritis. Pathophysiology 2005; 12:153-165.
Silman AJ, MacGregor AJ, Thomson W, et al. Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol 1993; 32: 903-907.
Bowes J, Barton A. Recent advances in the genetics of RA susceptibility. Rheumatology (Oxford) 2008; 47: 399-402.
Okada Y, Wu D, Trynka G, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014; 506: 376-381.
Goulielmos GN, Zervou MI, Myrthianou E, et al. Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients. Gene 2016; 583: 90-101.
Kochi Y, Suzuki A, Yamamoto K. Genetic basis of rheumatoid arthritis: A current review. Biochem Biophys Res Commun 2014; 452: 254-262.
Noack M, Miossec P. Th17 and regulatory T cell balance in auto­immune and inflammatory diseases. Autoimmun Rev 2014; 13: 668-677.
Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep 2009; 11: 365-370.
Leipe J, Grunke M, Dechant C, et al. Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum 2010; 62: 2876-2885.
Kane A, Deenick EK, Ma CS, et al. STAT3 is a central regulator of lymphocyte differentiation and function. Curr Opin Immunol 2014; 28: 49-57.
Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 2008; 40: 955-962.
Tsoi LC, Spain SL, Knight J, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet 2012; 44: 1341-1348.
Jakkula E, Leppä V, Sulonen A-M, et al. Genome-wide association study in a high-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene. Am J Hum Genet 2010; 86: 285-291.
Burton PR, Clayton DG, Cardon LR, et al. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447: 661-678.
Cénit MC, Alcina A, Márquez A, et al. STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility. Genes Immun 2010; 11: 264-268.
Davidson SI, Liu Y, Danoy PA, et al. Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese. Ann Rheum Dis 2011; 70: 289-292.
Ma Z, Wang G, Chen X, et al. Association of STAT3 common variations with obesity and hypertriglyceridemia: protective and contributive effects. Int J Mol Sci 2014; 15: 12258-12269.
Slattery ML, Lundgreen A, Hines LM, et al. Genetic variation in the JAK/STAT/SOCS signaling pathway influences breast cancer-specific mortality through interaction with cigarette smoking and use of aspirin/NSAIDs: the Breast Cancer Health Disparities Study. Breast Cancer Res Treat 2014; 147: 145-158.
Signal Transducer and Activator of Transcription 3; STAT3. Available: http://www.omim.org/entry/1025....
Vogel TP, Milner JD, Cooper MA. The Ying and Yang of STAT3 in Human Disease. J Clin Immunol 2015; 35: 615-623.
Flanagan SE, Haapaniemi E, Russell MA, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet 2014; 46: 812-814.
Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 2009; 60: 1647-1656.
Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 2014; 13: 668-677.
Seddighzadeh M, Gonzalez A, Ding B, et al. Variants within STAT genes reveal association with anticitrullinated protein antibody-negative rheumatoid arthritis in 2 European populations. J Rheumatol 2012; 39: 1509-1516.
Xiao L, Muhali F-S, Cai T-T, et al. Association of single-nucleotide polymorphisms in the STAT3 gene with autoimmune thyroid disease in Chinese individuals. Funct Integr Genom 2013; 13: 455-461.
Yan R, Lin F, Hu C, Tong S. Association between STAT3 polymorphisms and cancer risk: a meta-analysis. Mol Genet Genomics 2015; 290: 2261-2270.
Hu K, Hou S, Jiang Z, et al. JAK2 and STAT3 Polymorphisms in a Han Chinese Population with Behçet’s Disease. Invest Opthalmol Vis Sci 2012; 53: 538-541.
Sato K, Shiota M, Fukuda S, et al. Strong Evidence of a Combination Polymorphism of the Tyrosine Kinase 2 Gene and the Signal Transducer and Activator of Transcription 3 Gene as a DNA-Based Biomarker for Susceptibility to Crohn’s Disease in the Japanese Population. J Clin Immunol 2009; 29: 815-825.
Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Journals System - logo
Scroll to top