Associations Between Cytokine Gene Polymorphisms and Rheumatoid Arthritis in Turkish Population

Overview

Journal North Clin Istanb

Publisher Kare Publishing

Specialty General Medicine

Date 2020 Dec 31

PMID 33381695

Citations 4

Authors

Burcu Yucel

Ceren Sumer

Ilhami Gok

Murat Karkucak

Emel Alemdaroglu

Fahri Ucar

Affiliations

Soon will be listed here.

Abstract

Objective: Various cytokine polymorphisms have been associated with genetic risk factors predisposing to Rheumatoid Arthritis (RA) in different populations. To predict the clinical outcome as well as response to therapy in RA, studies aimed to describe genetic markers. The present study aims to search for polymorphisms of 13 cytokine coding genes in the Eastern Black Sea Region of Turkey.

Methods: DNAs of 49 patients and 96 healthy bone marrow and kidney donors were isolated from peripheral blood samples. Genotyping was performed using the Heidelberg Cytokine Typing Tray kit. PCR products were visualized on an agarose gel, and results were analyzed using the interpretation scheme provided with the kit. Arlequin 3.5 software was used for statistical analysis.

Results: No positive association was found between allele frequencies and the disease. However, a negative association was found for the IL-A -889 C allele (p=0.02, OR=0.533, Wald's 95% CI=0.318-0.893). IL-12 -1188 CC (p=0.01, OR=3.667, Wald's 95% CI=1.246-10.786), IL-4 -1098 GT (p=0.02, OR=2.405, Wald's 95% CI=1.129-5.125) genotypes were found positively associated with the RA, while IL-4 -590 CT (p=0.02, OR=0.422, Wald's 95% CI=0.201-0.886) was found negatively associated with the disease. In addition, IL-6 GG haplotype was found positively associated with the RA (p=0.02, OR=1.880, Wald's 95% CI=1.086-3.254).

Conclusion: Our findings suggest that some polymorphisms of the IL-1A, IL-2, IL-4, IL-6 and IL-12 could be responsible for the susceptibility or protective to RA in our study population. Multi-centered and large numbers of subjects containing studies that search for cytokine polymorphisms will gather more information regarding the susceptibility to RA of Turkish patients.

Citing Articles

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References

Silman A, Pearson J . Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002; 4 Suppl 3:S265-72. PMC: 3240153. DOI: 10.1186/ar578. View

Orozco G, Gonzalez-Gay M, Paco L, Lopez-Nevot M, Guzman M, Pascual-Salcedo D . Interleukin 12 (IL12B) and interleukin 12 receptor (IL12RB1) gene polymorphisms in rheumatoid arthritis. Hum Immunol. 2005; 66(6):710-5. DOI: 10.1016/j.humimm.2005.02.004. View

McInnes I, Schett G . Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007; 7(6):429-42. DOI: 10.1038/nri2094. View

Ollier W, Thomson W . Population genetics of rheumatoid arthritis. Rheum Dis Clin North Am. 1992; 18(4):741-59. View

Li X, Chai W, Ni M, Xu M, Lian Z, Shi L . The effects of gene polymorphisms in interleukin-4 and interleukin-6 on the susceptibility of rheumatoid arthritis in a Chinese population. Biomed Res Int. 2014; 2014:265435. PMC: 3953475. DOI: 10.1155/2014/265435. View

Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K . Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014; 506(7488):376-81. PMC: 3944098. DOI: 10.1038/nature12873. View

Park H, Kim S, Kweon H, Lee K, Valan Arasu M, Kim Y . Promoter polymorphism (-590, T/C) of interleukin 4 () gene is associated with rheumatoid arthritis: An updated meta-analysis. Saudi J Biol Sci. 2017; 24(2):444-449. PMC: 5272927. DOI: 10.1016/j.sjbs.2016.01.013. View

Kim W, Min S, Cho M, Youn J, Min J, Lee S . The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA). Clin Exp Immunol. 1999; 119(1):175-81. PMC: 1905529. DOI: 10.1046/j.1365-2249.2000.01095.x. View

Bax M, Heemst J, Huizinga T, Toes R . Genetics of rheumatoid arthritis: what have we learned?. Immunogenetics. 2011; 63(8):459-66. PMC: 3132380. DOI: 10.1007/s00251-011-0528-6. View

10.

Rego-Perez I, Fernandez-Moreno M, Blanco F . Gene polymorphisms and pharmacogenetics in rheumatoid arthritis. Curr Genomics. 2009; 9(6):381-93. PMC: 2691664. DOI: 10.2174/138920208785699553. View

11.

Magyari L, Varszegi D, Kovesdi E, Sarlos P, Farago B, Javorhazy A . Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications. World J Orthop. 2014; 5(4):516-36. PMC: 4133458. DOI: 10.5312/wjo.v5.i4.516. View

12.

Srirangan S, Choy E . The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2012; 2(5):247-56. PMC: 3383508. DOI: 10.1177/1759720X10378372. View

13.

Mateen S, Zafar A, Moin S, Khan A, Zubair S . Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta. 2016; 455:161-71. DOI: 10.1016/j.cca.2016.02.010. View

14.

Lee Y, Bae S . Associations between interleukin-1 and IL-1 receptor antagonist polymorphisms and susceptibility to rheumatoid arthritis: A meta-analysis. Cell Mol Biol (Noisy-le-grand). 2016; 61(8):105-11. View

15.

Barrera P, Faure S, Prudhomme J, Balsa A, Migliorini P, Chimenti D . European genetic study on rheumatoid arthritis: is there a linkage of the interleukin-1 (IL-1), IL-10 or IL-4 genes to RA?. Clin Exp Rheumatol. 2002; 19(6):709-14. View

16.

Haukim N, Bidwell J, Smith A, Keen L, Gallagher G, Kimberly R . Cytokine gene polymorphism in human disease: on-line databases, supplement 2. Genes Immun. 2002; 3(6):313-30. DOI: 10.1038/sj.gene.6363881. View

17.

Isomaki P, Punnonen J . Pro- and anti-inflammatory cytokines in rheumatoid arthritis. Ann Med. 1998; 29(6):499-507. DOI: 10.3109/07853899709007474. View

18.

Kurko J, Besenyei T, Laki J, Glant T, Mikecz K, Szekanecz Z . Genetics of rheumatoid arthritis - a comprehensive review. Clin Rev Allergy Immunol. 2013; 45(2):170-9. PMC: 3655138. DOI: 10.1007/s12016-012-8346-7. View

19.

Lagha A, Zidi S, Stayoussef M, Gazouani E, Kochkar R, Kochbati S . Interleukin-1β, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphisms in Tunisian patients with rheumatoid arthritis. Pathol Biol (Paris). 2015; 63(4-5):179-84. DOI: 10.1016/j.patbio.2015.04.004. View

20.

Excoffier L, Lischer H . Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour. 2011; 10(3):564-7. DOI: 10.1111/j.1755-0998.2010.02847.x. View