DOI QR코드

DOI QR Code

Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group

  • Park, Jin Woo (Division of Gastroenterology, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine) ;
  • Choi, Ja Sung (Division of Gastroenterology, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine) ;
  • Han, Ki Joon (Division of Gastroenterology, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine) ;
  • Lee, Sang Heun (Division of Gastroenterology, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine) ;
  • Kim, Eui Joo (Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center) ;
  • Cho, Jae Hee (Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center)
  • Received : 2017.03.14
  • Accepted : 2017.05.29
  • Published : 2018.11.01

Abstract

Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin $1{\beta}$ (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor ${\alpha}$ (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). Conclusions: IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

Keywords

References

  1. Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet 2015;386:85-96. https://doi.org/10.1016/S0140-6736(14)60649-8
  2. Johnson CD, Besselink MG, Carter R. Acute pancreatitis. BMJ 2014;349:g4859. https://doi.org/10.1136/bmj.g4859
  3. Tukiainen E, Kylanpaa ML, Puolakkainen P, et al. Polymorphisms of the TNF, CD14, and HSPA1B genes in patients with acute alcohol-induced pancreatitis. Pancreas 2008;37:56-61. https://doi.org/10.1097/MPA.0b013e31815d9bad
  4. Yin YW, Sun QQ, Feng JQ, Hu AM, Liu HL, Wang Q. Influence of interleukin gene polymorphisms on development of acute pancreatitis: a systematic review and meta-analysis. Mol Biol Rep 2013;40:5931-5941. https://doi.org/10.1007/s11033-013-2700-6
  5. Lee KJ, Kim HM, Choi JS, Kim YJ, Kim YS, Cho JH. Comparison of predictive systems in severe acute pancreatitis according to the revised Atlanta Classification. Pancreas 2016;45:46-50. https://doi.org/10.1097/MPA.0000000000000433
  6. Cho JH, Choi JS, Hwang ET, et al. Usefulness of scheduled follow-up CT in discharged patients with acute pancreatitis. Pancreatology 2015;15:642-646. https://doi.org/10.1016/j.pan.2015.09.004
  7. Cho JH, Jeon TJ, Choi JS, et al. EUS finding of geographic hyperechoic area is an early predictor for severe acute pancreatitis. Pancreatology 2012;12:495-501. https://doi.org/10.1016/j.pan.2012.08.007
  8. de-Madaria E, Martinez J, Sempere L, et al. Cytokine genotypes in acute pancreatitis: association with etiology, severity, and cytokine levels in blood. Pancreas 2008;37:295-301. https://doi.org/10.1097/MPA.0b013e31816726d5
  9. Mayer J, Rau B, Gansauge F, Beger HG. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut 2000;47:546-552. https://doi.org/10.1136/gut.47.4.546
  10. Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. Am J Surg 1998;175:76-83. https://doi.org/10.1016/S0002-9610(97)00240-7
  11. Banks PA. Epidemiology, natural history, and predictors of disease outcome in acute and chronic pancreatitis. Gastrointest Endosc 2002;56(6 Suppl):S226-S230. https://doi.org/10.1016/S0016-5107(02)70016-3
  12. Bishehsari F, Sharma A, Stello K, et al. TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis. Pancreatology 2012;12:113-118. https://doi.org/10.1016/j.pan.2012.02.014
  13. Smithies AM, Sargen K, Demaine AG, Kingsnorth AN. Investigation of the interleukin 1 gene cluster and its association with acute pancreatitis. Pancreas 2000;20:234-240. https://doi.org/10.1097/00006676-200004000-00003
  14. Stuber F, Petersen M, Bokelmann F, Schade U. A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis. Crit Care Med 1996;24:381-384. https://doi.org/10.1097/00003246-199603000-00004
  15. Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 1998;47:195-198. https://doi.org/10.1046/j.1365-3083.1998.00300.x
  16. Hu Z, Shao M, Chen Y, et al. Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer. Cancer Lett 2006;236:269-275. https://doi.org/10.1016/j.canlet.2005.05.015
  17. Xue H, Lin B, Ni P, Xu H, Huang G. Interleukin-1B and interleukin-1 RN polymorphisms and gastric carcinoma risk: a meta-analysis. J Gastroenterol Hepatol 2010;25:1604-1617. https://doi.org/10.1111/j.1440-1746.2010.06428.x
  18. Cho JH, Choi JS, Chun SW, Lee S, Han KJ, Kim HM. The IL-1B genetic polymorphism is associated with aspirin-induced peptic ulcers in a Korean ethnic group. Gut Liver 2016;10:362-368.
  19. El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000;404:398-402. https://doi.org/10.1038/35006081
  20. Carrol ED, Payton A, Payne D, et al. The IL1RN promoter rs4251961 correlates with IL-1 receptor antagonist concentrations in human infection and is differentially regulated by GATA-1. J Immunol 2011;186:2329-2335. https://doi.org/10.4049/jimmunol.1002402
  21. Tarlow JK, Blakemore AI, Lennard A, et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 1993;91:403-404.
  22. Mansfield JC, Holden H, Tarlow JK, et al. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology 1994;106:637-642. https://doi.org/10.1016/0016-5085(94)90696-3
  23. Tarlow JK, Clay FE, Cork MJ, et al. Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene. J Invest Dermatol 1994;103:387-390. https://doi.org/10.1111/1523-1747.ep12395398
  24. Blakemore AI, Cox A, Gonzalez AM, et al. Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus. Hum Genet 1996;97:369-374. https://doi.org/10.1007/BF02185776
  25. Reiner AP, Wurfel MM, Lange LA, et al. Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. Arterioscler Thromb Vasc Biol 2008;28:1407-1412. https://doi.org/10.1161/ATVBAHA.108.167437
  26. Formela LJ, Galloway SW, Kingsnorth AN. Inflammatory mediators in acute pancreatitis. Br J Surg 1995;82:6-13. https://doi.org/10.1002/bjs.1800820105
  27. Yin YW, Hu AM, Sun QQ, et al. Association between tumor necrosis factor-alpha gene -308A/G polymorphism and the risk of acute pancreatitis: a meta-analysis. J Surg Res 2012;178:409-414. https://doi.org/10.1016/j.jss.2012.02.001
  28. Powell JJ, Fearon KC, Siriwardena AK, Ross JA. Evidence against a role for polymorphisms at tumor necrosis factor, interleukin-1 and interleukin-1 receptor antagonist gene loci in the regulation of disease severity in acute pancreatitis. Surgery 2001;129:633-640. https://doi.org/10.1067/msy.2001.113375
  29. Schneider A, Pogue-Geile K, Barmada MM, Myers-Fong E, Thompson BS, Whitcomb DC. Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-alpha) promoter region or the TNF receptor 1 (TNFR1) gene. Genet Med 2003;5:120-125. https://doi.org/10.1097/01.GIM.0000055199.32817.CA
  30. Zhang DL, Zheng HM, Yu BJ, Jiang ZW, Li JS. Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock. World J Gastroenterol 2005;11:4409-4413. https://doi.org/10.3748/wjg.v11.i28.4409

Cited by

  1. Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats vol.25, pp.11, 2018, https://doi.org/10.3390/molecules25112493
  2. Mapping leprosy‐associated coding variants of interleukin genes by targeted sequencing vol.99, pp.6, 2018, https://doi.org/10.1111/cge.13945