OCTNs: Will the Real IBD5 Gene Please Stand Up?

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2006 Jun 15

PMID 16773684

Citations 9

Authors

Mark-S Silverberg

Affiliations

Soon will be listed here.

Abstract

Crohn's disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with a substantial heritable component. The IBD5 region on chromosome 5q31 is one of only two loci widely confirmed to be associated with Crohn's disease in multiple independent cohorts. Although many populations have demonstrated association with IBD5, there remains uncertainty as to the causal variant within the region. A recent report identified polymorphisms in SLC22A4 (OCTN1) and SLC22A5 (OCTN2) as being responsible for the IBD5 association, however, these findings have not been replicated. This review discusses the data evaluating the IBD5 locus and the OCTN genes and their relationship to inflammatory bowel disease. Several other genes, including IRF1 and P4HA2 may be equally as likely to contain the IBD5 causal variant as the OCTN genes.

Citing Articles

Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk.

Reshef Y, Finucane H, Kelley D, Gusev A, Kotliar D, Ulirsch J Nat Genet. 2018; 50(10):1483-1493.

PMID: 30177862 PMC: 6202062. DOI: 10.1038/s41588-018-0196-7.

Role of genetics in the diagnosis and prognosis of Crohn's disease.

Tsianos E, Katsanos K, Tsianos V World J Gastroenterol. 2012; 17(48):5246-59.

PMID: 22219593 PMC: 3247688. DOI: 10.3748/wjg.v17.i48.5246.

Selective regulation of cardiac organic cation transporter novel type 2 (OCTN2) in dilated cardiomyopathy.

Grube M, Ameling S, Noutsias M, Kock K, Triebel I, Bonitz K Am J Pathol. 2011; 178(6):2547-59.

PMID: 21641380 PMC: 3124333. DOI: 10.1016/j.ajpath.2011.02.020.

Human genetic factors and respiratory syncytial virus disease severity.

Miyairi I, DeVincenzo J Clin Microbiol Rev. 2008; 21(4):686-703.

PMID: 18854487 PMC: 2570150. DOI: 10.1128/CMR.00017-08.

The 5q31 variants associated with psoriasis and Crohn's disease are distinct.

Li Y, Chang M, Schrodi S, Callis-Duffin K, Matsunami N, Civello D Hum Mol Genet. 2008; 17(19):2978-85.

PMID: 18614543 PMC: 2536504. DOI: 10.1093/hmg/ddn196.

References

Torok H, Glas J, Tonenchi L, Lohse P, Muller-Myhsok B, Limbersky O . Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease. Gut. 2005; 54(10):1421-7. PMC: 1774699. DOI: 10.1136/gut.2005.066340. View

Russell R, Drummond H, Nimmo E, Anderson N, Noble C, WILSON D . Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease. Gut. 2006; 55(8):1114-23. PMC: 1856267. DOI: 10.1136/gut.2005.082107. View

Latiano A, Palmieri O, Valvano R, DInca R, Vecchi M, Ferraris A . Contribution of IBD5 locus to clinical features of IBD patients. Am J Gastroenterol. 2006; 101(2):318-25. DOI: 10.1111/j.1572-0241.2006.00389.x. View

Mirza M, Fisher S, King K, Cuthbert A, Hampe J, Sanderson J . Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn disease. Am J Hum Genet. 2003; 72(4):1018-22. PMC: 1180331. DOI: 10.1086/373880. View

Vasiliauskas E, Plevy S, Landers C, Binder S, Ferguson D, Yang H . Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup. Gastroenterology. 1996; 110(6):1810-9. DOI: 10.1053/gast.1996.v110.pm8964407. View

Ma Y, Ohmen J, Li Z, Bentley L, McElree C, Pressman S . A genome-wide search identifies potential new susceptibility loci for Crohn's disease. Inflamm Bowel Dis. 1999; 5(4):271-8. DOI: 10.1097/00054725-199911000-00005. View

Yamazaki K, Takazoe M, Tanaka T, Ichimori T, Saito S, Iida A . Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease. J Hum Genet. 2004; 49(12):664-668. DOI: 10.1007/s10038-004-0204-x. View

Palmieri O, Latiano A, Valvano R, DInca R, Vecchi M, Sturniolo G . Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. 2006; 23(4):497-506. DOI: 10.1111/j.1365-2036.2006.02780.x. View

Hugot J, Laurent-Puig P, Gower-Rousseau C, Olson J, Lee J, Beaugerie L . Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 1996; 379(6568):821-3. DOI: 10.1038/379821a0. View

10.

Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y . Lack of common NOD2 variants in Japanese patients with Crohn's disease. Gastroenterology. 2002; 123(1):86-91. DOI: 10.1053/gast.2002.34155. View

11.

Halfvarson J, Bodin L, Tysk C, Lindberg E, Jarnerot G . Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology. 2003; 124(7):1767-73. DOI: 10.1016/s0016-5085(03)00385-8. View

12.

Thompson N, Driscoll R, Pounder R, Wakefield A . Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ. 1996; 312(7023):95-6. PMC: 2349773. DOI: 10.1136/bmj.312.7023.95. View

13.

McGovern D, van Heel D, Negoro K, Ahmad T, Jewell D . Further evidence of IBD5/CARD15 (NOD2) epistasis in the susceptibility to ulcerative colitis. Am J Hum Genet. 2003; 73(6):1465-6. PMC: 1180410. DOI: 10.1086/379745. View

14.

Ogura Y, Bonen D, Inohara N, Nicolae D, Chen F, Ramos R . A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001; 411(6837):603-6. DOI: 10.1038/35079114. View

15.

Giallourakis C, Stoll M, Miller K, Hampe J, Lander E, Daly M . IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis. Am J Hum Genet. 2003; 73(1):205-11. PMC: 1180582. DOI: 10.1086/376417. View

16.

Orholm M, Munkholm P, Langholz E, Nielsen O, Sorensen T, Binder V . Familial occurrence of inflammatory bowel disease. N Engl J Med. 1991; 324(2):84-8. DOI: 10.1056/NEJM199101103240203. View

17.

Duerr R, Barmada M, Zhang L, Pfutzer R, Weeks D . High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12. Am J Hum Genet. 2000; 66(6):1857-62. PMC: 1378032. DOI: 10.1086/302947. View

18.

Rioux J, Silverberg M, Daly M, Steinhart A, McLeod R, Griffiths A . Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet. 2000; 66(6):1863-70. PMC: 1378042. DOI: 10.1086/302913. View

19.

Noble C, Nimmo E, Drummond H, Ho G, Tenesa A, Smith L . The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease. Gastroenterology. 2005; 129(6):1854-64. DOI: 10.1053/j.gastro.2005.09.025. View

20.

Economou M, Trikalinos T, Loizou K, Tsianos E, Ioannidis J . Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol. 2004; 99(12):2393-404. DOI: 10.1111/j.1572-0241.2004.40304.x. View