Analysis of Single Nucleotide Polymorphisms in the Region of CLDN2-MORC4 in Relation to Inflammatory Bowel Disease

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2013 Aug 16

PMID 23946598

Citations 7

Authors

Jan Soderman

Elisabeth Noren

Malin Christiansson

Hanna Bragde

Raphaele Thiebaut

Jean-Pierre Hugot

Curt Tysk

Colm A OMorain

Miquel Gassull

Yigael Finkel

Jean-Frederic Colombel

Marc Lemann

Sven Almer

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate a possible genetic influence of claudin (CLDN)1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.

Methods: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease -families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.

Results: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95%CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95%CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.

Conclusion: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

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References

McGovern D, Taylor K, Landers C, Derkowski C, Dutridge D, Dubinsky M . MAGI2 genetic variation and inflammatory bowel disease. Inflamm Bowel Dis. 2008; 15(1):75-83. PMC: 2614310. DOI: 10.1002/ibd.20611. View

Lo D, Tynan W, Dickerson J, Scharf M, Cooper J, Byrne D . Cell culture modeling of specialized tissue: identification of genes expressed specifically by follicle-associated epithelium of Peyer's patch by expression profiling of Caco-2/Raji co-cultures. Int Immunol. 2003; 16(1):91-9. DOI: 10.1093/intimm/dxh011. View

Sakaguchi T, Xiubin Gu , Golden H, Suh E, Rhoads D, Reinecker H . Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha. J Biol Chem. 2002; 277(24):21361-70. DOI: 10.1074/jbc.M110261200. View

Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K . A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007; 39(2):207-11. DOI: 10.1038/ng1954. View

Hugot J, Chamaillard M, Zouali H, Lesage S, Cezard J, Belaiche J . Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001; 411(6837):599-603. DOI: 10.1038/35079107. View

Howe K, Reardon C, Wang A, Nazli A, McKay D . Transforming growth factor-beta regulation of epithelial tight junction proteins enhances barrier function and blocks enterohemorrhagic Escherichia coli O157:H7-induced increased permeability. Am J Pathol. 2005; 167(6):1587-97. PMC: 1613202. DOI: 10.1016/s0002-9440(10)61243-6. View

Clayburgh D, Shen L, Turner J . A porous defense: the leaky epithelial barrier in intestinal disease. Lab Invest. 2004; 84(3):282-91. DOI: 10.1038/labinvest.3700050. View

Lesage S, Zouali H, Cezard J, Colombel J, Belaiche J, Almer S . CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002; 70(4):845-57. PMC: 379113. DOI: 10.1086/339432. View

Gullberg E, Soderholm J . Peyer's patches and M cells as potential sites of the inflammatory onset in Crohn's disease. Ann N Y Acad Sci. 2006; 1072:218-32. DOI: 10.1196/annals.1326.028. View

10.

Hollander D . Permeability in Crohn's disease: altered barrier functions in healthy relatives?. Gastroenterology. 1993; 104(6):1848-51. DOI: 10.1016/0016-5085(93)90668-3. View

11.

De La Vega F, Isaac H, Scafe C . A tool for selecting SNPs for association studies based on observed linkage disequilibrium patterns. Pac Symp Biocomput. 2006; :487-98. View

12.

Jostins L, Ripke S, Weersma R, Duerr R, McGovern D, Hui K . Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012; 491(7422):119-24. PMC: 3491803. DOI: 10.1038/nature11582. View

13.

Thjodleifsson B, Sigthorsson G, Cariglia N, Reynisdottir I, Gudbjartsson D, Kristjansson K . Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives?. Gastroenterology. 2003; 124(7):1728-37. DOI: 10.1016/s0016-5085(03)00383-4. View

14.

Munkholm P, Langholz E, Hollander D, Thornberg K, Orholm M, Katz K . Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives. Gut. 1994; 35(1):68-72. PMC: 1374635. DOI: 10.1136/gut.35.1.68. View

15.

Burke J, Mulsow J, OKeane C, Docherty N, Watson R, OConnell P . Fibrogenesis in Crohn's disease. Am J Gastroenterol. 2006; 102(2):439-48. DOI: 10.1111/j.1572-0241.2006.01010.x. View

16.

Vandewalle C, Comijn J, De Craene B, Vermassen P, Bruyneel E, Andersen H . SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Res. 2005; 33(20):6566-78. PMC: 1298926. DOI: 10.1093/nar/gki965. View

17.

Soderholm J, Olaison G, Lindberg E, Hannestad U, Vindels A, Tysk C . Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?. Gut. 1998; 44(1):96-100. PMC: 1760070. DOI: 10.1136/gut.44.1.96. View

18.

Vind I, Vieira A, Hougs L, Tavares L, Riis L, Andersen P . NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype-phenotype analysis in Danish and Portuguese patients and controls. Digestion. 2005; 72(2-3):156-63. DOI: 10.1159/000088371. View

19.

Teahon K, Smethurst P, Levi A, Menzies I, Bjarnason I . Intestinal permeability in patients with Crohn's disease and their first degree relatives. Gut. 1992; 33(3):320-3. PMC: 1373820. DOI: 10.1136/gut.33.3.320. View

20.

Maniatis N, Collins A, Xu C, McCarthy L, Hewett D, Tapper W . The first linkage disequilibrium (LD) maps: delineation of hot and cold blocks by diplotype analysis. Proc Natl Acad Sci U S A. 2002; 99(4):2228-33. PMC: 122347. DOI: 10.1073/pnas.042680999. View