Discs Large Homolog 5 (DLG5) Gene Polymorphism and Crohn’s Disease: A Meta-Analysis of the Published Studies

  • Arezoo Shafieyoun Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Sharareh Moraveji Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
  • Mohammad Bashashati Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA. AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), El Paso, TX, USA.
  • Nima Rezaei Mail Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Keywords:
Crohn’s disease, DLG5 protein, Gene polymorphism

Abstract

The real pathophysiology of Crohn’s disease is unknown. The higher prevalence of Crohn’s disease in Caucasian and Jewish ethnicities, as well as its familial aggregation and higher concordance among monozygotic twins, suggest some roles for genes in its development, clinical progression, and outcome. Recent original studies have indicated DLG5113G/A gene polymorphism as a risk factor for Crohn’s disease. Meanwhile, the results of these studies are not consistent. We performed the current meta-analysis to understand whether there is any association between DLG5 gene polymorphism and the risk of Crohn’s disease. PubMed was searched to find the case-control studies on DLG5 gene polymorphisms and Crohn’s disease. This search compiled 65 articles and based on our criteria. 11 articles were included in this meta-analysis. The association between the DLG5 113G/A polymorphism and the risk of disease was assessed using odds ratio (OR) and 95% confidence interval (95% CI). Heterogeneity was evaluated based on I2 values.  Random and fixed-effect models were used when I2>50% and I2≤50%, respectively. Eleven studies with a total of 4648 cases and 5677 controls were pooled. Based on our meta-analysis, DLG5113G/A gene polymorphism both at genotypic and allelic levels were not associated with the risk of Crohn’s disease. Pooled data indicated no significant association between DLG5113G/A gene polymorphism and the development of Crohn’s disease. In order to achieve a superior conclusion, multicenter studies on larger number of patients are recommended.

References

Lakatos PL. Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J Gastroenterol 2006;12(38):6102-8.

Freeman HJ. Application of the Montreal classification for Crohn's disease to a single clinician database of 1015 patients. Can J Gastroenterol, 2007;21(6):363-6.

Baumgart DC, Sandborn WJ. Crohn's disease. Lancet 2012;380(9853):1590-605.

Shanahan F. Crohn's disease. Lancet 2002;359(9300): 62-9.

Liu JZ. Anderson CA. Genetic studies of Crohn's disease:past, present and future. Best Pract Res Clin Gastroenterol 2014;28(3):373-86.

Sezaki T, Inada K, Sogabe T, et al. Role of Dlg5/lp-dlg, a membrane-associated guanylate kinase family protein, in epithelial-mesenchymal transition in LLc-PK1 renal epithelial cells. PLoS One 2012;7(4):e35519.

Humbert P, Russell S, Richardson H, Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer. Bioessays 2003;25(6):542-53.

Wakabayashi M, Ito T, Mitsushima M, et al. Interaction of lp-dlg/KIAA0583, a membrane-associated guanylate kinase family protein, with vinexin and beta-catenin at sites of cell-cell contact. J Biol Chem 2003;278(24):21709-14.

Stoll M, Corneliussen B, Costello CM, et al. Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 2004;36(5):476-80.

Yamazaki K, Takazoe M, Tanaka T, et al. Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease. J Hum Genet 2004;49(12):664-8.

Gazouli M, Mantzaris G, Archimandritis AJ, et al. Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease. World J Gastroenterol 2005;11(47):7525-30.

Torok HP, Glas J, Tonenchi L, et al. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease. Gut 2005;54(10):1421-7.

Medici V, Mascheretti S, Croucher PJ, et al. Extreme heterogeneity in CARD15 and DLG5 Crohn diseaseassociated polymorphisms between German and Norwegian populations. Eur J Hum Genet 2006;14(4):459-68.

Tremelling M, Waller S, Bredin F, et al. Genetic variants in TNF-alpha but not DLG5 are associated with inflammatory bowel disease in a large United Kingdom cohort. Inflamm Bowel Dis 2006;12(3):178-84.

Pearce AV, Fisher SA, Prescott NJ, et al. Investigation ofassociation of the DLG5 gene with phenotypes of inflammatory bowel disease in the British population. Int J Colorectal Dis 2007;22(4):419-24.

Buning C, Geerdts L, Fiedler T, et al. DLG5 variants in inflammatory bowel disease. Am J Gastroenterol 2006;101(4):786-92.

Lakatos PL, Ficsher S, Claes K, et al. DLG5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease. Inflamm Bowel Dis 2006;12(5):362-8.

Dema B, Fernández-Arquero M, Maluenda C, et al. The R30Q DLG5 variant is not associated with celiac disease or inflammatory bowel disease in the Spanish population. Tissue Antigens 2011;77(1):62-4.

Noble CL, Nimmo ER, Drummond H, et al. DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population. Gut2005;4(10):1416-20.

Lin Z, Poritz L, Franke A, et al. Genetic association of DLG5 R30Q with familial and sporadic inflammatory bowel disease in men. Dis Markers 2009;27(5):193-201.

Browning BL, Huebner C, Petermann I, et al. Association of DLG5 variants with inflammatory bowel disease in the New Zealand Caucasian population and meta-analysis of the DLG5 R30Q variant. Inflamm Bowel Dis 2007;13(9):1069-76.

Weersma RK, Stokkers PC, van Bodegraven AA, et al. Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort. Gut 2009;58(3):388-95.

Daly MJ, Pearce AV, Farwell, et al. Association of DLG5 R30Q variant with inflammatory bowel disease. Eur J Hum Genet 2005;13(7):835-9.

Bashashati M, Rezaei N, Bashashati H, et al. Cytokine gene polymorphisms are associated with irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil 2012;24(12):1102-e566.

Shah G, Brugada R, Gonzalez O, et al. The cloning, genomic organization and tissue expression profile of the human DLG5 gene: Correction. BMC Genomics 2002;3:14.

Martin-Belmonte F, Perez-Moreno M. Epithelial cell polarity, stem cells and cancer. Nat Rev Cancer 2011;12(1):23-38.

Friedrichs F, Stoll M. Role of discs large homolog 5. World J Gastroenterol 2006;12(23):3651-6.

Nechiporuk T, Fernandez TE, Vasioukhin F. Failure of epithelial tube maintenance causes hydrocephalus andrenal cysts in Dlg5-/- mice. Dev Cell 2007;13(3):338-50.

Smolen GA., Zhang J, Zubrowski MJ, et al. A genomewide RNAi screen identifies multiple RSK-dependent regulators of cell migration. Genes Dev 2010;24(23):2654-65.

Taniuchi K, Nakagawa H, Nakamura T, et al. Downregulation of RAB6KIFL/KIF20A, a kinesin involved with membrane trafficking of discs large homologue 5, can attenuate growth of pancreatic cancer cell. Cancer Res 2005;65(1):105-12.

Yamamoto-Furusho JK, Mendivil EJ, Fonseca-Camarillo G, et al. Increased expression of discs large homolog 5 gene (DLG5) in ulcerative colitis patients compared to healthy individuals. Inflamm Bowel Dis 2011;17(7):1639.

Friedrichs F, Brescianini S, Annese V, et al. Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in men. Hum Genet 2006;119(3):305-11.

Chua KH, Lian LH, Kee BP, et al. Identification of DLG5 and SLC22A5 gene polymorphisms in Malaysian patients with Crohn's disease. J Dig Dis 2011;12(6):459-66.

Lin Z, Hegarty JP, Berb A, et al. DLG5 P1371Q is associated with inflammatory bowel disease and complementary to R30Q in disease susceptibility. Swiss Med Wkly 2011;141: w13290.

Taher M, Ebrahimi Daryani N, Hedayat M, et al. RAC1 single nucleotide polymorphisms in Crohn's disease. Clin Res Hepatol Gastroenterol 2014;38(4):e75-7.

Daryani NE, Sadr M, Moossavi S, et al. Significance of IL-1RA polymorphism in Iranian patients with inflammatory bowel disease. Dig Dis Sci 2015;60(5):1389-95.

Najmi Varzandeh F, Farhadi E, Ebrahimi Daryani N, et al. Interleukin-23 receptor single nucleotide polymorphisms in Crohn's disease. Clin Res Hepatol Gastroenterol 2015;39(4):e51-3.

Published
2016-05-28
How to Cite
1.
Shafieyoun A, Moraveji S, Bashashati M, Rezaei N. Discs Large Homolog 5 (DLG5) Gene Polymorphism and Crohn’s Disease: A Meta-Analysis of the Published Studies. Acta Med Iran. 54(5):289-295.
Section
Review Article(s)