Allele and genotype frequency of single nucleotide polymorphisms presented in genes of immune response related to risk of Inflammatory Bowel Disease in Mexican population.

Abstract

Event Abstract Back to Event Allele and genotype frequency of single nucleotide polymorphisms presented in genes of immune response related to risk of Inflammatory Bowel Disease in Mexican population. Rita S. Quiroz Cruz1*, Ali B. Posada Reyes1*, Jerusalen Islas Arenas1* and Salvador Fonseca Coronado1* 1 Universidad Nacional Autónoma de México, Unidad de investigación Multidisciplinaria, Mexico Inflammatory Bowel Disease (IBD) is characterized by the presence of chronic inflammation with two clinical forms: Crohn's disease (CD) and ulcerative colitis (UC). In Mexico, there are no conclusive data although it is estimated that incidence of UC is 0.2%- 4.89%, while EC incidence is estimated between 0.0008% and 1.11%. IBD includes gastrointestinal symptoms such as diarrhea, abdominal pain, rectal bleeding or extra-intestinal manifestations that delay diagnosis. Pathogenesis of IBD is complex. It has been proposed that inflammation is triggered by an impaired immune response against intestinal microbiota, which in turn could be promoted by environmental factors in genetically susceptible individuals. Among the genetic factors involved, there are several single nucleotide polymorphisms (SNP) associated in the susceptibility to IBD progression. The first genetic risk factors associated to IBD were the SNPs rs2066844 and rs2066845 located in the NOD-2 gene. NOD-2 is a pattern recognition receptor (PRR) that is responsible for the detection of intracellular bacteria and is activated through recognition of muramyl-dipeptide, thereby maintaining homeostasis in the intestinal mucosa. These SNPs are located in the coding region for LRR domain (Leucine-Rich Repeat) of NOD-2, therefor affecting recognition of their ligand, which allow to bacterial proliferation and a decrease of immune tolerance towards commensal microorganisms; CT and TT genotype of SNP rs2066844 has been associated with susceptibility to IBD as well as GC and CC genotype of rs2066845. The SNP present in the gene coding for a protein involved in the process of autophagy; ATG16L1 (rs2241880) has also been associated with the development of IBD. Autophagy is a process responsible for intracellular degradation agents and cellular homeostasis. Given the importance of autophagy in restricting the growth of certain microorganisms, mutations affecting the proteins involved in this process, result in the reduced elimination of pathogens or commensal. The SNP rs2241880 (GG) results in reduced ability to form autophagosome, thereby increasing the risk of development of IBD. It has also been studied the rs11209026 present in the gene of IL-23 receptor (IL-23R); IL-23 is involved in the activation of the inflammatory Th17 response. The presence of the AA genotype affects a cellular signaling from IL-23R, resulting in a poor inflammatory response, so this polymorphism has been associated with protection to the development of the disease. Meanwhile, SNPs present in regions of the gene coding for IL-10 has also been identified: IL-10 is an immune regulatory cytokine that acts on antigen presenting cells by inhibiting both the synthesis of pro-inflammatory and costimulatory molecules, thus decreasing the response immune against commensal microorganisms creating an atmosphere of tolerance. It has been observed that patients with an impaired production of IL-10 have severe UC and CD. SNP rs1800896 present in the promoter region of the IL-10 seem to generate genetic variations which affect cytokine levels. The AA genotype has been associated with the risk of developing IBD and the decreased production of IL-10. This association has also been described with a SNP located near to the 3'UTR of the IL10 gene (rs3024505). The rs3024505 is located in an intergenic region of the gene of IL-10, this region has regulatory sequences, which can regulate the expression of IL-10. The CT and TT genotype has been associated with susceptibility to develop IBD. In this work we analyze the SNPs present in NOD-2 (rs2066844, rs2066845), ATG16L1 (rs2241880), IL-23R (rs11209026) and IL-10 (rs1800896, rs3024505) genes using TaqMan® PCR assay (Applied Biosystems) for detection of these SNPs. 400 donors of Mexico City and their metropolitan area were analyzed to determine the allele and genotype frequency of these SNPs. For the SNP rs2066844 located in NOD-2, CC, CT and TT genotypes were presented in 92.5, 7.5 and 0%, respectively; while for the rs2066845, genotype distribution were GG, GC and CC of 96.75, 3.25 and 0%, respectively. The rs2241880 present in ATG16L1 show 60, 34.5 and 5.5% for the AA, AG and GG genotypes respectively. Genotype distributions for SNP rs11209026 located in IL-23R were 68.5, 29 and 2.5% for GG, AG and AA respectively. Finally for the SNP rs1800896 in the IL-10 gene, the AA, AG and GG genotype frequency were 59.25, 34.5 and 6.25% respectively. For the same gene, the rs3024505 show a distribution of 92.5, 6.75 and 0.75% for CC, CT and TT respectively. According to the Hardy-Weinberg equilibrium, SNPs rs2066844 (p = 0.435) and rs2066845 (p = 0.741) of NOD-2 gene, SNP rs2241880 of ATG16L1 gene (p = 0.712), SNP rs11209026 of the IL-23R gene (p = 0.580) and SNP rs1800896 (p = 0.418) of the IL-10 gene, are good candidates for use as biological markers in the implementation of a predictive model of the development of IBD population of Mexico City and Metropolitan Area. The rs3024505 (p = 0.003) gene IL-10 do not comply with such equilibrium, however, the sample size should be increased in future studies to confirm these observations. The risk of progression to severe forms of the disease could be reduced with the use of clinical, serological and genetic markers which facilitate the diagnosis; we propose the implementation of a predictive model of evolution of the disease based on the analysis of SNPs present in NOD-2, ATG16L1, IL-23R and IL-10 genes that helps the diagnosis of IBD in Mexican Population. Acknowledgements This work was supported by: Project TA200214 Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica, DGAPA, UNAM. References Alvarez- Lobos y cols., 2005. Crohn´s disease patiens carrying NOD2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence. Ann Surg. 242:693-700. Andersen y cols., 2010. The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study. BMC Medical Genetics. 11:82. Cho J. 2008. The genetics and inmunopathogenesis of inflammatory bowel disease. Nat Rev Immunol. 8(6): 458-466. Colombel JF y cols., 2010. Infliximab, azathioprine, or combination terapy for Crohn´s disease. N Engl J Med. 362: 1383-1395. Gazouli M y cols., 2010. NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn’s disease. World Journal Gastroenterology. 16(14): 1753-1758. Kabi y cols., 2012. Digesting the Genetics of Inflammatory Bowel Disease – Insights from Studies of Autophagy Risk Genes. Inflamm Bowel Dis. 18(4): 782-792. Kaser A y cols., 2010. Genes and Environment: How will our concepts on the pathophysiology of IBD develop in the future? Digestive Diseases. 28: 395-405. Levine B, Deretic V. 2007. Unveiling the roles of autophagy in innate and adaptative immunity. Nature Rev. Immunology. 7: 767-777. Podolsky DK. 2002. Inflammatory bowel disease. N Engl J Med. 347: 417-429. Yamazaki K y cols., 2002. Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patiens with Crohn´s disease. J Hum Genet. 47(9): 469-72. Erratum in: J Hum Genet. 48(7): 397. Keywords: IBD, snps, Hardy-Weinberg equilibrium, Genetic Markers, diagnosis, TaqMan PCR Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Mucosal Immunity and the microbiome Citation: Quiroz Cruz RS, Posada Reyes AB, Islas Arenas J and Fonseca Coronado S (2015). Allele and genotype frequency of single nucleotide polymorphisms presented in genes of immune response related to risk of Inflammatory Bowel Disease in Mexican population.. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00247 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 May 2015; Published Online: 14 Sep 2015. * Correspondence: Miss. Rita S Quiroz Cruz, Universidad Nacional Autónoma de México, Unidad de investigación Multidisciplinaria, México, México, Mexico, sarai_quiroz_1208@hotmail.com Miss. Ali B Posada Reyes, Universidad Nacional Autónoma de México, Unidad de investigación Multidisciplinaria, México, México, Mexico, bereniceposadareyes@yahoo.com.mx Miss. Jerusalen Islas Arenas, Universidad Nacional Autónoma de México, Unidad de investigación Multidisciplinaria, México, México, Mexico, jerusalen.islas@gmail.com Dr. Salvador Fonseca Coronado, Universidad Nacional Autónoma de México, Unidad de investigación Multidisciplinaria, México, México, Mexico, fonsecacoronado@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rita S Quiroz Cruz Ali B Posada Reyes Jerusalen Islas Arenas Salvador Fonseca Coronado Google Rita S Quiroz Cruz Ali B Posada Reyes Jerusalen Islas Arenas Salvador Fonseca Coronado Google Scholar Rita S Quiroz Cruz Ali B Posada Reyes Jerusalen Islas Arenas Salvador Fonseca Coronado PubMed Rita S Quiroz Cruz Ali B Posada Reyes Jerusalen Islas Arenas Salvador Fonseca Coronado Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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