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NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene polymorphisms in Turkish patients with inflammatory bowel disease

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Abstract

Purpose

The genetic susceptibility of people with certain NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene variants to inflammatory bowel disease is still under investigation. The aim of this study was to investigate polymorphisms in the NOD2/CARD15 (R702W, G908R, and 3020insC), NOD1/CARD4 (E266K, D372N), and ICAM-1 (G241R, K469E) genes, which are known to be associated with inflammation, in Turkish patients with inflammatory bowel disease and healthy control groups.

Methods

The genotypes of 70 patients with endoscopically and histopathologically diagnosed Crohn's disease (38 men, 32 women; mean age, 38.8 ± 1.3), 120 patients with ulcerative colitis (67 men, 53 women; mean age, 41.7 ± 1.3) and 106 healthy control subjects (37 men, 69 women; mean age, 35.7 ± 1.4), who stated that they had never had any prior bowel disease history, were compared. A polymerase chain reaction-restriction fragment length polymorphism analysis was performed for two variants of the ICAM-1 gene, the three main variants of the NOD2/CARD15 gene, and the E266K variant of the NOD1/CARD4 gene, and DNA sequencing was used for the D372N polymorphism of the NOD1/CARD4 gene.

Results

In this study, the three previously described Crohn's disease-predisposing variants of the NOD2/CARD15 gene and the polymorphisms examined in the NOD1/CARD4 and ICAM-1 genes were not found to be associated with ulcerative colitis or Crohn's disease.

Conclusions

These findings suggest that the polymorphisms observed in the NOD2/CARD15, NOD1/CARD4, and ICAM-1 genes are not genetic susceptibility factors for Crohn's disease or ulcerative colitis in Turkey.

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References

  1. M Orholm P Munkholm E Langholz OH Nielsen IA Sorensen V Binder (1991) ArticleTitleFamilial occurrence of inflammatory bowel disease N Engl J Med 324 84–8 Occurrence Handle1984188 Occurrence Handle1:STN:280:DyaK3M%2FnsVagtw%3D%3D Occurrence Handle10.1056/NEJM199101103240203

    Article  PubMed  CAS  Google Scholar 

  2. J Satsangi WMC Rosenberg DP Jewell (1994) ArticleTitleThe prevalence of inflammatory bowel disease in relatives of patients with Crohn's disease Eur J Gastroenterol Hepatol 6 413–6

    Google Scholar 

  3. M Peeters H Nevens P Baert M Hiele AM De Meyer R Vlietinck et al. (1996) ArticleTitleFamilial aggregation in Crohn's disease: increased age-adjusted risk and concordance in clinical characteristic Gastroenterology 11 597–03 Occurrence Handle10.1053/gast.1996.v111.pm8780562

    Article  Google Scholar 

  4. NP Thompson R Driscoll RE Pounder AJ Wakefield (1996) ArticleTitleGenetics versus environment in inflammatory bowel disease: results of a British twin study BMJ 312 95–6 Occurrence Handle8555939 Occurrence Handle1:STN:280:DyaK287ktF2huw%3D%3D

    PubMed  CAS  Google Scholar 

  5. J Subhani SM Montgomery RE Ounder AJ Wakefield (1998) ArticleTitleConcordance rates of twins and siblings in inflammatory bowel disease Gut 42 A40

    Google Scholar 

  6. JP Hugot P Laurent-Puig C Gower-Rousseaf JM Olson JC Lee L Beaugerie et al. (1996) ArticleTitleMapping of susceptibility locus for Crohn's disease on chromosome 16 Nature 379 821–3 Occurrence Handle8587604 Occurrence Handle1:CAS:528:DyaK28XhsVWlu7Y%3D Occurrence Handle10.1038/379821a0

    Article  PubMed  CAS  Google Scholar 

  7. Y Ogura N Inohara A Benito FF Chen S Yamaoka G Nunez (2001) ArticleTitleNOD2, a NOD1/Apaf-1 family member that is restricted to monocytes and activates NFκB J Biol Chem 276 4812–8 Occurrence Handle11087742 Occurrence Handle1:CAS:528:DC%2BD3MXhtlOqtL8%3D Occurrence Handle10.1074/jbc.M008072200

    Article  PubMed  CAS  Google Scholar 

  8. JP Hugot M Chamaillard H Zouali S Lesage JP Cezard J Belaiches et al. (2001) ArticleTitleAssociation of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease Nature 411 599–603 Occurrence Handle11385576 Occurrence Handle1:CAS:528:DC%2BD3MXksVShtLY%3D Occurrence Handle10.1038/35079107

    Article  PubMed  CAS  Google Scholar 

  9. Y Ogura DK Bonen N Inohara DL Nicola FF Chen R Ramos et al. (2001) ArticleTitleA frameshift mutation in NOD2 associated with susceptibility to Crohn's disease Nature 411 603–6 Occurrence Handle11385577 Occurrence Handle1:CAS:528:DC%2BD3MXksVShur8%3D Occurrence Handle10.1038/35079114

    Article  PubMed  CAS  Google Scholar 

  10. J Hampe A Cuthbert PJ Croucher MM Mirza S Mascheretti S Fisher et al. (2001) ArticleTitleAssociation between insertion mutation in NOD2 gene and Crohn's disease in German and British populations Lancet 357 1925–8 Occurrence Handle11425413 Occurrence Handle1:CAS:528:DC%2BD3MXks1OisLk%3D Occurrence Handle10.1016/S0140-6736(00)05063-7

    Article  PubMed  CAS  Google Scholar 

  11. S Lesage H Zouali JP Cezard JF Colombel J Belaiche S Almer et al. (2002) ArticleTitleCARD15/NOD2 mutational analysis and genotype–phenotype correlation in 612 patients with inflammatory bowel disease Am J Hum Genet 70 845–57 Occurrence Handle11875755 Occurrence Handle1:CAS:528:DC%2BD38XivFClurw%3D Occurrence Handle10.1086/339432

    Article  PubMed  CAS  Google Scholar 

  12. AP Cuthbert SA Fisher MM Mirza K King JC Hampe PJ Roucher et al. (2002) ArticleTitleThe contribution of NOD2 gene mutations to the risk and site of disease in Inflammatory bowel disease Gastroenterology 122 867–74 Occurrence Handle11910337 Occurrence Handle1:CAS:528:DC%2BD38XjtFOmtbY%3D Occurrence Handle10.1053/gast.2002.32415

    Article  PubMed  CAS  Google Scholar 

  13. DK Bonen Y Ogura DL Nicolae N Inohara L Saab T Tanabe et al. (2003) ArticleTitleCrohn's disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan Gastroenterology 124 140–6 Occurrence Handle12512038 Occurrence Handle1:CAS:528:DC%2BD3sXot1amsg%3D%3D Occurrence Handle10.1053/gast.2003.50019

    Article  PubMed  CAS  Google Scholar 

  14. K Yamazaki M Takazoe T Tanaka T Kazumori Y Nakamura (2002) ArticleTitleAbsence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn's disease J Hum Genet 47 469–72 Occurrence Handle12202985 Occurrence Handle1:CAS:528:DC%2BD38Xnt1WhsLk%3D Occurrence Handle10.1007/s100380200067

    Article  PubMed  CAS  Google Scholar 

  15. N Inoue K Tamura Y Kinouchi Y Fukuda S Takahashi Y Ogura et al. (2002) ArticleTitleLack of common NOD2 variants in Japanese patients with Crohn's disease Gastroenterology 123 86–91 Occurrence Handle12105836 Occurrence Handle1:CAS:528:DC%2BD38Xmt1aiu70%3D Occurrence Handle10.1053/gast.2002.34155

    Article  PubMed  CAS  Google Scholar 

  16. RWL Leong A Armuzzi T Ahmad ML Wong P Tse DP Jewell et al. (2003) ArticleTitleNOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population Aliment Pharmacol Ther 17 1465–70 Occurrence Handle12823148 Occurrence Handle1:CAS:528:DC%2BD3sXmt1Ogtbo%3D Occurrence Handle10.1046/j.1365-2036.2003.01607.x

    Article  PubMed  CAS  Google Scholar 

  17. JP Croucher S Mascheretti J Hampe K Huse H Frenzel M Stoll et al. (2003) ArticleTitleHaplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations Eur J Hum Genet 11 6–16 Occurrence Handle12529700 Occurrence Handle1:CAS:528:DC%2BD3sXht12hurs%3D Occurrence Handle10.1038/sj.ejhg.5200897

    Article  PubMed  CAS  Google Scholar 

  18. J Bertin WJ Nir CM Fischer OV Tayber PR Errada JR Grant et al. (1999) ArticleTitleHuman CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-κB J Biol Chem 274 12955–8 Occurrence Handle10224040 Occurrence Handle1:CAS:528:DyaK1MXjtFOmuro%3D Occurrence Handle10.1074/jbc.274.19.12955

    Article  PubMed  CAS  Google Scholar 

  19. N Inohara T Koseki L del Peso Y Hu C Yee S Chen et al. (1999) ArticleTitleNod1, an Apaf-1 like activator of caspase-9 and nuclear factor-κB J Biol Chem 274 14560–7 Occurrence Handle10329646 Occurrence Handle1:CAS:528:DyaK1MXks1Krurk%3D Occurrence Handle10.1074/jbc.274.21.14560

    Article  PubMed  CAS  Google Scholar 

  20. SE Girardin IG Boneca J Viala M Chamaillard A Labigne G Thomas et al. (2003) ArticleTitleNOD2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection J Biol Chem 278 8869–72 Occurrence Handle12527755 Occurrence Handle1:CAS:528:DC%2BD3sXhvVyqsbs%3D Occurrence Handle10.1074/jbc.C200651200

    Article  PubMed  CAS  Google Scholar 

  21. N Inohara Y Ogura A Fontalba O Gutierrez F Pons J Crespo et al. (2003) ArticleTitleHost recognition of bacterial muramyl dipeptide mediated through NOD2: implication for Crohn's disease J Biol Chem 278 5509–12 Occurrence Handle12514169 Occurrence Handle1:CAS:528:DC%2BD3sXht1aqsro%3D Occurrence Handle10.1074/jbc.C200673200

    Article  PubMed  CAS  Google Scholar 

  22. J Satsangi M Parkers E Louis L Hashimoto N Kato K Welsh et al. (1996) ArticleTitleTwo stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosome 3, 7 and 12 Nat Genet 14 199–02 Occurrence Handle8841195 Occurrence Handle1:CAS:528:DyaK28XmtVKntLc%3D Occurrence Handle10.1038/ng1096-199

    Article  PubMed  CAS  Google Scholar 

  23. H Zouali S Lesage F Merlin JP Cezard JF Colombel J Belaiche et al. (2003) ArticleTitleCARD4/NOD1 is not involved in inflammatory bowel disease Gut 52 71–4 Occurrence Handle12477763 Occurrence Handle1:CAS:528:DC%2BD3sXmtVyqsA%3D%3D Occurrence Handle10.1136/gut.52.1.71

    Article  PubMed  CAS  Google Scholar 

  24. JD Rioux MS Silverberg MJ Daly (2000) ArticleTitleGenome wide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci Am J Hum Genet 66 1863–70 Occurrence Handle10777714 Occurrence Handle1:CAS:528:DC%2BD3cXntV2jurw%3D Occurrence Handle10.1086/302913

    Article  PubMed  CAS  Google Scholar 

  25. DK Vora CR Rosenbloom AL Beaudet RW Cottingham (1994) ArticleTitlePolymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster Genomics 21 473–7 Occurrence Handle7525451 Occurrence Handle1:CAS:528:DyaK2MXitVeltw%3D%3D Occurrence Handle10.1006/geno.1994.1303

    Article  PubMed  CAS  Google Scholar 

  26. JE Lennard-Jones (1989) ArticleTitleClassification of inflammatory bowel disease Scand J Gastroenterol Suppl 24 2–6

    Google Scholar 

  27. SM Aljanabi I Martinez (1997) ArticleTitleUniversal and rapid salt-extraction of high quality genomic DNA for PCR-based techniques Nucleic Acids Res 25 4692–3 Occurrence Handle9358185 Occurrence Handle1:CAS:528:DyaK1cXhsFWrsA%3D%3D Occurrence Handle10.1093/nar/25.22.4692

    Article  PubMed  CAS  Google Scholar 

  28. T Heliö L Halme M Lappalainen H Fostad P Paavola-Sakki M Faerkkilae et al. (2003) ArticleTitleCARD15/NOD2 gene variants are associated with familially occurring and complicated forms of Crohn's disease Gut 52 558–62 Occurrence Handle12631669 Occurrence Handle10.1136/gut.52.4.558

    Article  PubMed  Google Scholar 

  29. RA Gbadegesin CJ Watson SA Cotton PEC Brenchley NJA Webb (2002) ArticleTitleA PCR-RFLP typing method for adhesion molecule gene polymorphisms and allele frequencies in a normal UK population Eur J Immunol 29 109–11 Occurrence Handle1:CAS:528:DC%2BD38XivFCqsLw%3D Occurrence Handle10.1046/j.1365-2370.2002.00277.x

    Article  CAS  Google Scholar 

  30. JP Hugot (2004) ArticleTitleInflammatory bowel disease: a complex group of genetic disorders Best Pract Res Clin Gastroenterol 18 451–62 Occurrence Handle15157820 Occurrence Handle10.1016/j.bpg.2004.01.001

    Article  PubMed  Google Scholar 

  31. DPB McGovern P Hysi T Ahmad DA van Heel MF Moffatt A Carey et al. (2005) ArticleTitleAssociation between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease Hum Mol Genet 14 1245–50 Occurrence Handle15790594 Occurrence Handle1:CAS:528:DC%2BD2MXktFyqsb8%3D Occurrence Handle10.1093/hmg/ddi135

    Article  PubMed  CAS  Google Scholar 

  32. P Hysi MF Kabesch M Schedel D Carr Y Zhang B Boardman et al. (2005) ArticleTitleNOD1 variation, immunoglobulin E and asthma Hum Mol Genet 14 935–41 Occurrence Handle15718249 Occurrence Handle1:CAS:528:DC%2BD2MXis1yjt7k%3D Occurrence Handle10.1093/hmg/ddi087

    Article  PubMed  CAS  Google Scholar 

  33. P Joling S Boom J Johnson ME Cekker JG Van Den Twell HJ Schuurman (1994) ArticleTitleDomain 5 of the intercellular adhesion molecule-1 (ICAM-1) is involved in adhesion of B-cells and follicular dendritic cells Adv Exp Med Biol 355 131–5 Occurrence Handle7709811 Occurrence Handle1:CAS:528:DyaK2MXivFWqtLg%3D

    PubMed  CAS  Google Scholar 

  34. H Yang DK Vora SR Targan (1995) ArticleTitleIntercellular adhesion molecule 1 gene associations with immunologic subsets of inflammatory bowel disease Gastroenterology 109 440–8 Occurrence Handle7615193 Occurrence Handle1:CAS:528:DyaK2MXntlCgtL0%3D Occurrence Handle10.1016/0016-5085(95)90331-3

    Article  PubMed  CAS  Google Scholar 

  35. J Matsuzawa K Sugimura Y Matsuda M Takazoe K Ishizuka T Mochizuki et al. (2003) ArticleTitleAssociation between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population Gut 52 75–8 Occurrence Handle12477764 Occurrence Handle1:CAS:528:DC%2BD3sXmtVyqsQ%3D%3D Occurrence Handle10.1136/gut.52.1.75

    Article  PubMed  CAS  Google Scholar 

  36. C Braun R Zahn K Martin E Albert C Folwaczny (2001) ArticleTitlePolymorphisms of the ICAM-1 gene are associated with inflammatory bowel disease, regardless of the p-ANCA status Clin Immunol 101 357–60 Occurrence Handle11726228 Occurrence Handle1:CAS:528:DC%2BD38XkvFKhtg%3D%3D Occurrence Handle10.1006/clim.2001.5118

    Article  PubMed  CAS  Google Scholar 

  37. C Salvarani B Casali L Boiardi A Ranzi P Macchioni D Nicoli et al. (2000) ArticleTitleIntercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell artheritis: association with disease risk and severity J Rheumatol 27 1251–21

    Google Scholar 

  38. L Boiardi C Salvarani B Casali I Olivieri G Ciancio F Cantini et al. (2001) ArticleTitleIntercellular adhesion molecule-1 gene polymorphisms in Behçet's disease J Rheumatol 28 1283–7 Occurrence Handle11409120 Occurrence Handle1:CAS:528:DC%2BD3MXkvVOhu7c%3D

    PubMed  CAS  Google Scholar 

  39. AJ Mclaren SE Marshall NA Haldar CG Mullighan SV Fuggle PJ Morris et al. (1999) ArticleTitleAdhesion molecule polymorphisms in chronic renal allograft failure Kidney Int 55 1977–82 Occurrence Handle10231462 Occurrence Handle1:STN:280:DyaK1M3ltV2lsA%3D%3D Occurrence Handle10.1046/j.1523-1755.1999.00427.x

    Article  PubMed  CAS  Google Scholar 

  40. DH Verity RW Vaughan E Kondeatis W Madanat H Zureikat F Fayyad et al. (2000) ArticleTitleIntercellular adhesion molecule-1 gene polymorphisms in Behçet's disease Eur J Immunol 27 73–6 Occurrence Handle1:CAS:528:DC%2BD3cXjsFCrtLk%3D Occurrence Handle10.1046/j.1365-2370.2000.00202.x

    Article  CAS  Google Scholar 

  41. M Nishimura H Obayashi E Maruya (2000) ArticleTitleAssociation between type 1 diabetes age-at-onset and intercellular adhesion molecule-1 gene polymorphism Hum Immunol 6 507–10 Occurrence Handle10.1016/S0198-8859(00)00101-4

    Article  Google Scholar 

  42. A Papa R Pola A Flex S Danese A Armuzzi E Gaetani et al. (2004) ArticleTitlePrevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease Dig Liver Dis 36 528–32 Occurrence Handle15334773 Occurrence Handle1:CAS:528:DC%2BD2cXnt1Kqs7o%3D Occurrence Handle10.1016/j.dld.2004.03.015

    Article  PubMed  CAS  Google Scholar 

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Özen, S., Daǧlı, Ü., Kiliç, M. et al. NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene polymorphisms in Turkish patients with inflammatory bowel disease. J Gastroenterol 41, 304–310 (2006). https://doi.org/10.1007/s00535-005-1780-z

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