Hamid Asadzadeh AGHDAEI,
Elnaz EMAMI,
Mahyar NOURIAN,
Vahid CHALESHI,
Peyman TARBAN,
Hedieh BALAII,
Pedram AZIMZADEH,
Shiva IRANI,
Shabnam SHAHROKH,
Mohammad ROSTAMI-NEJAD,
Mohammad Reza ZALI
8840
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.
___
- 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.