Top

BMC Medical Genetics

Published in:

Open Access 01-12-2012 | Research article

Influence of IL17A polymorphisms on the aberrant methylation of DAPK and CDH1 in non-cancerous gastric mucosa

Authors: Tomiyasu Arisawa, Tomomitsu Tahara, Mikihiro Tsutsumi, Tomoyuki Shibata

Published in: BMC Medical Genetics | Issue 1/2012

Abstract

Background

CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of IL-17 in inflammatory response to H. pylori colonization has been indicated. We investigated the influence of IL17A polymorphisms, -197 G > A (rs2275913) and *1249 C > T (rs3748067), on the methylation of DAPK and CDH1.

Methods

Gastric mucosal samples were obtained from 401 subjects without malignancies. Methylation status of gene was determined by MSP. The genotyping of IL17A was performed by PCR-SSCP.

Results

Methylations of DAPK and CDH1 were seen in 196 and 149 of all 401 subjects, respectively. Overall, *1249 T carrier was associated with a decreased risk for DAPK methylation, whereas -197 G > A was not. In the subjects older than 60 years old, *1249 T carrier was more strongly associated with gene methylation and -197 A carrier tended to be associated with an increased risk for CDH1 methylation. When evaluating by inflammation promoting haplotype (-197 mutant carrier with *1249 homozygote), this haplotype had a more strongly increased risk for both DAPK and CDH1 methylations in comparatively older subjects. Both atrophy and metaplasia scores were significantly increased with age in -197 A carrier or *1249 CC homozygote, whereas were not in -197 GG homozygote or *1249 T carrier. PG I/II ratio was more significantly decreased in -197 A carrier than in GG homozygote under influence of H. pylori infection.

Conclusions

In -197 A allele carrier with *1249 CC homozygote, the methylations of both DAPK and CDH1 may be increased gradually, but more rapidly than the other genotypes, with age and altered gastric mucosal structure induced by H. pylori infection.

Available only for authorised users

Rutitzky LI, da Rosa JR L, Stadecker MJ: Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol. 2005, 175: 3920-3926.CrossRefPubMed

Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL: Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003, 278: 1910-1914. 10.1074/jbc.M207577200.CrossRefPubMed

Kolls JK, Linden A: Interleukin-17 family members and inflammation. Immunity. 2004, 21: 467-476. 10.1016/j.immuni.2004.08.018.CrossRefPubMed

Fossiez F, Banchereau J, Murray R, Van Kooten C, Garrone P, Lebecque S: Interleukin-17. Int Rev Immunol. 1998, 16: 541-551.CrossRefPubMed

Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP: IL-17 stimulates the production and expression of proinflammatory and hematopoietic cytokines, IL-1b and TNF-a, by human macrophages. J Immunol. 1998, 160: 3513-3521.PubMed

Laan M, Cui ZH, Hoshino H, Lotvall J, Sjostrand M, Gruenert DC, Skoogh BE, Linden A: Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. J Immunol. 1999, 162: 2347-2352.PubMed

Luzza F, Parrello T, Monteleone G, Sebkova L, Romano M, Zarrilli R, Imeneo M, Pallone F: Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa. J Immunol. 2000, 165: 5332-5337.CrossRefPubMed

Sebkova L, Pellicano A, Monteleone G, Grazioli B, Guarnieri G, Imeneo M, Pallone F, Luzza F: Extracellular signal-regulated protein kinase mediates interleukin 17 (IL-17)-induced IL-8 secretion in Helicobacter pylori-infected human gastric epithelial cells. Infect Immun. 2004, 72: 5019-5026. 10.1128/IAI.72.9.5019-5026.2004.CrossRefPubMedPubMedCentral

Mizuno T, Ando T, Nobata K, Tsuzuki T, Maeda O, Watanabe O, Minami M, Ina K, Kusugami K, Peek RM, Goto H: Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization. World J Gastroenterol. 2005, 11: 6305-6311.CrossRefPubMedPubMedCentral

10.

Shiomi S, Toriie A, Imamura S, Konishi H, Mitsufuji S, Iwakura Y, Yamaoka Y, Ota H, Yamamoto T, Imanishi J, Kita M: IL-17 is involved in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model. Helicobacter. 2008, 13: 518-524. 10.1111/j.1523-5378.2008.00629.x.CrossRefPubMedPubMedCentral

11.

Parkin DM, Bray F, Ferlay J, Pisani P: (2005) Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108. 10.3322/canjclin.55.2.74.CrossRefPubMed

12.

Kamangar F, Dores GM, Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006, 24: 2137-2150. 10.1200/JCO.2005.05.2308.CrossRefPubMed

13.

Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK: Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991, 325: 1127-1131. 10.1056/NEJM199110173251603.CrossRefPubMed

14.

Blaser MJ, Parsonnet J: Parasitism by the ‘slow’ bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J Clin Invest. 1994, 94: 4-8. 10.1172/JCI117336.CrossRefPubMedPubMedCentral

15.

Huang JQ, Sridhar S, Chen Y, Hunt RH: Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998, 114: 1169-1179. 10.1016/S0016-5085(98)70422-6.CrossRefPubMed

16.

Esteller M, Corn PG, Baylin SB, Herman JG: A gene hypermethylation profile of human cancer. Cancer Res. 2001, 61: 3225-3229.PubMed

17.

Tahara T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, Okubo M, Yonemura J, Maeda Y, Maruyama N, Kamano T, Kamiya Y, Fujita H, Nakagawa Y, Nagasaka M, Iwata M, Hirata I, Arisawa T: Increased Number of CpG Island Hypermethylation in Tumor Suppressor Genes of Non-Neoplastic Gastric Mucosa Correlates with Higher Risk of Gastric Cancer. Digestion. 2010, 82: 27-36. 10.1159/000252766.CrossRefPubMed

18.

Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB: Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994, 4: 536-540.CrossRef

19.

Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP: Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res. 1998, 23: 5489-5494.

20.

Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA: Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res. 2001, 61: 3573-3577.PubMed

21.

Bian YS, Osterheld MC, Fontolliet C, Bosman FT, Benhattar J: p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Gastroenterology. 2001, 122: 1113-1121.CrossRef

22.

Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M, Tamura G, Saito D, Sugimura T, Ichinose M, Ushijima T: High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006, 12: 989-995. 10.1158/1078-0432.CCR-05-2096.CrossRefPubMed

23.

Tahara T, Arisawa T, Sibata T, Wang FY, Nakamura M, Sakata M, Nagasaka M, Takagi T, Kamiya Y, Fujita H, Nakamura M, Hasegawa S, Iwata M, Takahama K, Watanabe M, Hirata I, Nakano H: Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium. Digestion. 2007, 75: 54-61. 10.1159/000101775.CrossRefPubMed

24.

Kang GH, Lee HJ, Hwang KS, Lee S, Kim JH, Kim JS: Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation. Am J Pathol. 2003, 163: 1551-1556. 10.1016/S0002-9440(10)63511-0.CrossRefPubMedPubMedCentral

25.

Kang GH, Lee S, Lim JS, Jung HY: Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. Lab Invest. 2003, 83: 635-641.CrossRefPubMed

26.

Tahara T, Arisawa T, Shibata T, Nakamura M, Yoshioka D, Okubo M, Maruyama N, Kamano T, Kamiya Y, Fujita H, Nakagawa Y, Nagasaka M, Iwata M, Takahama K, Watanabe M, Yamashita H, Hirata I: Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis. Eur J Gastroenterol Hepatol. 2009, 21: 613-619. 10.1097/MEG.0b013e32830e28b2.CrossRefPubMed

27.

Shibata T, Tahara T, Hirata I, Arisawa T: Genetic polymorphism of interleukin-17A and -17F genes in gastric carcinogenesis. Hum Immunol. 2009, 70: 547-551. 10.1016/j.humimm.2009.04.030.CrossRefPubMed

28.

Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, Fujita H, Nakamura M, Yoshioka D, Arima Y, Okubo M, Hirata I, Nakano H: The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol. 2008, 28: 44-49. 10.1007/s10875-007-9125-8.CrossRefPubMed

29.

Nordang GBN, Viken MK, Hollis-Moffatt JE, Merriman TR, Forre OT, Helgetveit K, Kvien TK, Lie BA: Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology. 2009, 48: 367-370. 10.1093/rheumatology/ken512.CrossRefPubMed

30.

Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y, Chen M, Sung JJ, Hu P: Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer. 2010, 127: 86-92. 10.1002/ijc.25027.CrossRefPubMed

31.

Chen J, Deng Y, Zhao J, Luo Z, Peng W, Yang J, Ren L, Wang L, Fu Z, Yang X, Liu E: The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis. J Clin Immunol. 2010, 30: 539-545. 10.1007/s10875-010-9391-8.CrossRefPubMed

32.

Katzenellenbogen RA, Baylin SB, Herman JG: Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood. 1999, 93: 4347-4353.PubMed

33.

Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996, 93: 9821-9826. 10.1073/pnas.93.18.9821.CrossRefPubMedPubMedCentral

34.

Dixon MF, Genta RM, Yardley JH, Correa P: Classification and grading of gastritis: the updated Sydney system. Am J Surg Pathol. 1996, 20: 1161-1181.CrossRefPubMed

35.

Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG: CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res. 2001, 61: 2847-2851.PubMed

36.

Pestov DG, Strezoska Z, Lau LF: Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G(1)/S transition. Mol Cell Biol. 2001, 21: 4246-4255. 10.1128/MCB.21.13.4246-4255.2001.CrossRefPubMedPubMedCentral

37.

Tahara T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, Okubo M, Yonemura J, Maeda Y, Maruyama N, Kamano T, Kamiya Y, Fujita H, Nakagawa Y, Nagasaka M, Iwata M, Hirata I, Arisawa T: Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa. Int J Mol Med. 2009, 24: 563-569.CrossRefPubMed

38.

Tahara T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, Okubo M, Maruyama N, Kamano T, Kamiya Y, Fujita H, Nakagawa Y, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I, Arisawa T: MTHFR 677T carrier influences the methylation status of H. Pylori-infected gastric mucosa in older subject. Dig Dis Sci. 2009, 54: 2391-2398. 10.1007/s10620-008-0624-0.CrossRefPubMed

39.

Correa P: Human gastric carcinogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992, 52: 6735-6740.PubMed

40.

Kaise M, Yamasaki T, Yonezawa J, Miwa J, Ohta Y, Tajiri H: CpG island hypermethylation of tumor-suppressor genes in H. pylori - infected non-neoplastic gastric mucosa is linked with gastric cancer risk. Helicobacter. 2008, 13: 35-41.CrossRefPubMed

41.

Nakajima T, Maekita T, Oda I, Gotoda T, Yamamoto S, Umemura S, Ichinose M, Sugimura T, Ushijima T, Saito D: Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Cancer Epidemiol Biomarkers Prev. 2006, 15: 2317-2321. 10.1158/1055-9965.EPI-06-0436.CrossRefPubMed

42.

Pietrowski E, Bender B, Huppert J, White R, Luhmann HJ, Kuhlmann CRW: Pro-inflammatory effects of interleukin-17A on vascular smooth muscle cells involve NAD(P)Hoxidase derived reactive oxygen species. J Vasc Res. 2011, 48: 52-58. 10.1159/000317400.CrossRefPubMed

43.

Weitzman SA, Turk PW, Milkowski D, Kozlowski K: Free radical adducts induce alterations in DNA cytosine methylation. Proc Natl Acad Sci USA. 1994, 91: 1261-1264. 10.1073/pnas.91.4.1261.CrossRefPubMedPubMedCentral

44.

Ouyang W, Kolls JK, Zheng Y: The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008, 28: 454-467. 10.1016/j.immuni.2008.03.004.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/13/59/prepub

Title: Influence of IL17A polymorphisms on the aberrant methylation of DAPK and CDH1 in non-cancerous gastric mucosa
Authors: Tomiyasu Arisawa
Tomomitsu Tahara
Mikihiro Tsutsumi
Tomoyuki Shibata
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2012
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-13-59

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Influence of IL17A polymorphisms on the aberrant methylation of DAPK and CDH1 in non-cancerous gastric mucosa

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

Low prevalence of connexin-40 gene variants in atrial tissues and blood from atrial fibrillation subjects

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

Cheek swabs, SNP chips, and CNVs: Assessing the quality of copy number variant calls generated with subject-collected mail-in buccal brush DNA samples on a high-density genotyping microarray

Functional effects of the TMEM43 Ser358Leu mutation in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy

PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients

Genetic variants associated with breast size also influence breast cancer risk