Interleukin 12B mRNA level and rs3212227 genotyping in peripheral blood mononuclear cells of inflammatory bowel disease patients

  Background/aim: Inflammatory bowel disease (IBD) is a multifactorial disorder. Single nucleotide polymorphisms (SNPs) in the IL-12 gene, which are the main factors to regulate the immune reaction, play an important role in the production of IL-12 molecules. The aim of this study was to evaluate the correlation between the SNP on position +1188 of the 3 ' UTR region of the IL-12 p40 subunit gene and expression of the IL-12 p40 gene. Materials and methods: This case-control study was performed with 102 patients with IBD and 107 healthy people. PCR-RFLP and comparative real-time PCR were performed to assess the association between genotype and IL-12 gene expression. Results: The frequency of AA, CA, and CC genotypes of this gene at position +1188 was calculated to be 58.8%, 32.4%, and 8.8% in patients and 61.7%, 26.2%, and 12.1% in the control group, respectively, with no significant difference between the two groups (IL- 12B rs3212227: AA (Reference 1), CA (P = 0.407); OR (95% CI) 0.771 (0.418-1.424), CC (P = 0.561); OR (95% CI) 1.313 (0.524-3.292)). Also, the IL-12B mRNA expression level was compared between IBD patients and healthy controls and demonstrated a significant association (R 2 0.136, 95% CI 1.892-3.872, P < 0.0001). Conclusion: Our results show that IL-12B expression in IBD may be associated with altered immune and inflammatory responses.

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  • Hammer T, Nielsen KR, Munkholm P, Burisch J, Lynge E. The Faroese IBD study–incidence of inflammatory bowel diseases across 54 years of population-based data. J Crohn Colitis 2016; 10: 934-942.
  • Jelsness-Jørgensen LP, Frigstad SO, Moum B, Grimstad T, Opheim R, Jahnsen J, Bernklev T. Pain may be an important factor to consider in inflammatory bowel disease patients troubled by fatigue. United Eur Gastroent 2017; 5: 687-693.
  • Balaii H, Asadzadeh Aghdaei H, Farnood A, Habibi M, Mafi AA, Firouzi F, Sharifian A, Shahrokh S, Lahmi F, Zojaji H et al. Time trend analysis and demographic features of inflammatory bowel disease in Tehran. Gastroenterology and Hepatology from Bed to Bench 2014; 8: 253-261.
  • Alinaghi S, Chaleshi V, Ghavami SB, Balaii H, Azimzadeh P, Kadijani AA, Nourian M, Shahrokh S, Asgharian AM, Aghdaei HA et al. Comparative evaluation of IL-16 mRNA level and rs1131445 polymorphism of IL-16 gene in peripheral blood mononuclear cells of patients with inflammatory bowel diseases. South Asian Journal of Experimental Biology 2017; 6: 212-219.
  • Leppkes M, Neurath MF, Herrmann M, Becker C. Immune deficiency vs. immune excess in inflammatory bowel diseases— STAT3 as a rheo-STAT of intestinal homeostasis. J Leukocyte Biol 2016; 99: 57-66.
  • Tang C, Kamiya T, Kadoki M, Iwakura Y. A novel role of Dectin-1 signaling in promoting intestinal inflammation. Cytokine 2012; 59: 516.
  • Nourian M, Chaleshi V, Pishkar L, Azimzadeh P, Baradaran Ghavami S, Balaii H, Alinaghi S, Shahrokh S, Asadzadeh Aghdaei H, Zali MR. Evaluation of tumor necrosis factor (TNF)-α mRNA expression level and the rs1799964 polymorphism of the TNF-α gene in peripheral mononuclear cells of patients with inflammatory bowel diseases. Biomed Rep 2017; 6: 698-702.
  • Kamada N, Rogler G. The innate immune system: a trigger for many chronic inflammatory intestinal diseases. Inflammatory Intestinal Diseases 2016; 1: 70-77.
  • Kaser A, Pasaniuc B. IBD genetics: focus on (dys) regulation in immune cells and the epithelium. Gastroenterology 2014; 146: 896-899.
  • Basso PJ, Fonseca MT, Bonfá G, Alves VB, Sales-Campos H, Nardini V, Cardoso CR. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease. Braz J Med Biol Res 2014; 47: 727-377.
  • Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006; 12: S3-S9.
  • Ananthakrishnan AN. Environmental triggers for inflammatory bowel disease. Current Gastroenterology Reports 2013; 15: 1-7.
  • Guariso G, Gasparetto M, Day AS, Henderson P. Epidemiology and natural history of IBD in the paediatric age. Gastroent Res Pract 2014; 2014: 432807.
  • Opstelten JL, Beelen RM, Leenders M, Hoek G, Brunekreef B, van Schaik FD, et al. Exposure to ambient air pollution and the risk of inflammatory bowel disease: a European nested case– control study. Digest Dis Sci 2016; 61: 2963-2971.
  • Safarpour AR, Hosseini SV, Mehrabani D. Epidemiology of inflammatory bowel diseases in iran and Asia; a mini review. Iranian Journal of Medical Sciences 2013; 38: 140.
  • Malekzadeh F, Alberti C, Nouraei M, Vahedi H, Zaccaria I, Meinzer U, Nasseri-Moghaddam S, Sotoudehmanesh R, Momenzadeh S, Khaleghnejad R et al. Crohn’s disease and early exposure to domestic refrigeration. PLoS One 2009; 4: e4288.
  • Rogler G, Andus T. Cytokines in inflammatory bowel disease. World J Surg 1998; 22: 382-389.
  • Cho JH, Brant SR. Recent insights into the genetics of inflammatory bowel disease. Gastroenterology 2011; 140: 1704-1712.
  • Shokrgozar MA SS, Amirzargar AA, Shokri F, Rezaei N, Arjang Z. IL-2, IFN-γ, and IL-12 gene polymorphisms and susceptibility to multiple sclerosis. J Clin Immunol 2009; 29: 747-751.
  • Sallusto F. Heterogeneity of human CD4+ T cells against microbes. Annu Rev Immunol 2016; 34: 317-334.
  • Troegeler A, Mercier I, Cougoule C, Pietretti D, Colom A, Duval C, Vu Manh TP, Capilla F, Poincloux R, Pingris K et al. C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells. P Natl Acad Sci USA 2017; 114: E540-E549.
  • Curran SA, Shyer JA, St Angelo ET, Talbot LR, Sharma S, Chung DJ, Heller G, Hsu KC, Betts BC, Young JW. Human dendritic cells mitigate NK-cell dysfunction mediated by nonselective JAK1/2 blockade. Caner Immunol Res 2017; 5: 52-62.
  • Wei XQ, Rogers H, Lewis MA, Williams DW. The role of the IL-12 cytokine family in directing T-cell responses in oral candidosis. Clin Dev Immunol 2011; 2011: 697340.
  • Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011; 474: 307-317.
  • Shui JW, Kronenberg M. HVEM is a TNF receptor with multiple regulatory roles in the mucosal immune system. Immune Network 2014; 14: 67-72.
  • Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
  • Hsieh CS MS, Tripp CS, Wolf SF, O’Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria -induced macrophages. J Immunol 1993; 260: 547-549.
  • Schmidt C, Giese T, Ludwig B, Mueller-Molaian I, Marth T, Zeuzem S, Meuer SC, Stallmach A. Expression of interleukin- 12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn’s disease but not in ulcerative colitis. Inflamm Bowel Dis 2005; 11: 16-23.
  • Hamza T, Barnett JB, Li B. Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci 2010; 11: 789-806.
  • Yan J, Smyth MJ, Teng MW. Interleukin (IL)-12 and IL-23 and their conflicting roles in cancer. CSH Perspect Biol 2017; 10: a028530.
  • Márquez AMJ, Taxonera C, Díaz-Rubio M, De La Concha EG, Urcelay E, Martínez A. IL23R and IL12B polymorphisms in Spanish IBD patients: no evidence of interaction. Inflamm Bowel Dis 2008; 14: 1192-1196.
  • Yamazaki KTA, Takazoe M, Kubo M, Onouchi Y, Fujino A, Kamatani N, Nakamura Y, Hata A. Positive association of genetic variants in the upstream region of NKX2-3 with Crohn’s disease in Japanese patients. Gastroenterology 2009; 58: 228-232.
  • Glas J, Seiderer J, Wagner J, Olszak T, Fries C, Tillack C, Friedrich M, Beigel F, Stallhofer J, Steib C et al. Analysis of IL12B gene variants in inflammatory bowel disease. PLoS One 2012; 7: e34349.
  • Bonyadi M, Abdolmohammadi R, Jahanafrooz Z, Somy MH, Khoshbaten M. TNF-alpha gene polymorphisms in Iranian Azari Turkish patients with inflammatory bowel diseases. Saudi J Gastroenterol 2014; 20: 108-112.
  • Chaleshi V, Tajali R, Savabkar S, Zali N, Mojarad EN, Haghazali M, Pasha S, Aghdaei HA, Zali MR, Vahedi M. Lack of association between NOD2 rs3135500 and IL12B rs1368439 microRNA binding site SNPs and colorectal cancer susceptibility in an Iranian population. MicroRNA 2016; 5: 152-156.
  • Eskandari‐Nasab E, Moghadampour M, Asadi‐Saghandi A, Kharazi‐Nejad E, Rezaeifar A, Pourmasoumi H. Levels of interleukin‐(IL)‐12p40 are markedly increased in brucellosis among patients with specific IL‐12B genotypes. Scand J Immunol 2013; 78: 85-91.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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