Irak-4 rs4251481 gene variant: as a risk factor on inflammatory bowel disease

Irak-4 rs4251481 gene variant: as a risk factor on inflammatory bowel disease

Background/aim: Abnormal immune response occurs in individuals who have alleles associated with innate and adaptive immunemechanisms that predispose to inflammatory bowel disease (IBD). Interleukin-1 receptor-associated kinase 4 (IRAK-4) involved inthe pathway produces cytokines that initiate and maintain inflammation through Toll-like receptors and interleukin-1 receptors on themembranes of innate immune cells are stimulated with antigens. It was aimed to investigate whether IRAK-4 rs3794262 and rs4251481polymorphisms predispose to IBD and the possible effects of these polymorphisms by examining these gene polymorphisms with theclinic and prognostic parameters of IBD.Material and methods: Real-time PCR technique was used to detect IRAK-4 polymorphisms in 107 patients with IBD and 103 healthycontrols.Results: As a result of experimental studies, the frequency of occurrence of rs4251481 polymorphism related AG genotype (P = 0.029)and G allele (P = 0.005) was found to increase statistically in patients compared to controls. In the control group, the rs4251481 AAgenotype rate of incidence increased compared with the patient group (P = 0.005).Conclusion: Consequently, this is the first study in terms of both polymorphisms on IBD. These results suggest that rs4251481 AGgenotype and G allele are associated with increased IBD risk in patients.

___

  • 1. Szigethy E, McLafferty L, Goyal A. Inflammatory bowel disease. Child Adolesc Psychiatr Clin N Am 2010; 19: 301-318.
  • 2. Loftus EV. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004; 126: 1504-1517.
  • 3. Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13: 3-10.
  • 4. Sarmento A. Editorial: Understanding Crohn’s Disease: immunity, genes and microbes. Front Immunol 2017; 8: 357.
  • 5. López-Hernández R, Valdés M, Campillo JA, MartínezGarcía P, Salama H, Bolarin JM, Martínez H, Moya-Quiles MR, Minguela A, Sánchez-Torres A et al. Pro- and antiinflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease. Int J Immunogenet 2015; 42: 38-45.
  • 6. Koziczak-Holbro M, Littlewood-Evans A, Pöllinger B, Kovarik J, Dawson J, Zenke G, Burkhart C, Müller M, Gram H. Essential role of IRAK-4 protein and its kinase activity in Toll-like receptormediated immune responses but not in TCR signaling. J Exp Med 2007; 204: 1013-1024.
  • 7. Zhang Y, Lin X, Desrosiers M. Association pattern of interleukin-1 receptor-associated kinase-4 gene polymorphisms with allergic rhinitis in a Han Chinese population. PLoS One 2011; 6: 21769.
  • 8. Koziczak-Holbro M, Littlewood-Evans A, Pöllinger B, Kovarik J, Dawson J, Zenke G, Burkhart C, Müller M, Gram H. The critical role of kinase activity of interleukin-1 receptor-associated kinase 4 in animal models of joint inflammation. Arthritis Rheum 2009; 60: 1661-1671.
  • 9. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448: 427-434.
  • 10. Suzuki N, Suzuki S, Yeh WC. IRAK-4 as the central TIR signaling mediator in innate immunity. Trends Immunol 2002; 23: 503-506.
  • 11. Kondo M, Tahara A, Hayashi K, Abe M, Inami H, Ishikawa T, Ito H, Tomura Y. Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats. Naunyn Schmiedebergs Arch Pharmacol 2004; 387: 909-919.
  • 12. Henriksen M, Jahnsen J, Lygren I, Stray N, Sauar J, Vatn MH, Moum B, IBSEN Study Group. C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study. Gut 2008; 57: 1518-1523.
  • 13. Sachar DB, Smith H, Chan S, Cohen LB, Lichtiger S, Messer J. Erythrocytic sedimentation rate as a measure of clinical activity in inflammatory bowel disease. J Clin Gastroenterol 1986; 8: 647-650.
  • 14. Menees SB, Powell C, Kurlander J, Goel A, Chey WD. A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. Am J Gastroenterol 2015; 110: 444-454.