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Su2075 Rs3761547 FOXP3 Polymorphism is Not Related to Celiac Disease
Su2075 Rs3761547 FOXP3 Polymorphism is Not Related to Celiac Disease Gloria Serena, Craig Sturgeon, Alessio Fasano
AGA Abstracts
Background: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically predisposed individuals. FOXP3 is the master regulator for the development and suppressive function of regulatory T cells, a minor subpopulation of CD4+ T cells Involved in regulation of immune response, maintaining immunological self-tolerance and immune homeostasis, including control of autoimmune diseases and cancer surveillance. Polymorphisms in foxp3 gene have been associated to several autoimmune diseases as autoimmune thyroid disease and systemic lupus erythematosus. The presence of polymorphisms in foxp3 gene could potentially alter the FOXP3 function and therefore potentially related to celiac disease onset. Aim: To detect potential correlation between foxp3 gene polymorphisms and the onset of celiac disease. Methods: DNA previously extracted from 6 celiac and 8 control patients was amplified by PCR. The foxp3 gene was then entirely sequenced and the obtained sequences compared with the foxp3 sequence in GENE BANK. From this screening analysis we were able to select one point mutation that seemed to be potentially associated with celiac disease (rs3761547), a polymorphism already associated with allergic rhinitis. We then proceeded with the specific screening for this polymorphism in 23 controls and 47 celiac patients.Results: The initial screening showed 50% of the celiac patients presenting the polymorphism rs3761547 while none of the controls presented it. These results lead us to screen a larger number of patients and controls for that specific polymorphism. This expanded analysis failed to reveal any difference between celiac patients and controls, with 20% of both controls and celiac patients showing the polymorphism. Conclusions: In this study we performed a screening of the entire foxp3 gene in order to detect polymorphisms potentially associated with the celiac disease onset. Our analysis didn't reveal any association between celiac disease and the presence of polymorphisms excluding a possible association of celiac disease with point mutations in foxp3.
Positive EPCAM immunostaining of intestinal biopsy. Enterocyte tufts are evident.
Su2076 Interleukin 23 Receptor, and ATG16L1 Gene Polymorphisms in Inflammatory Bowel Diseases, and the Association With the Clinical Course Gökhan Kabaçam, Senem C. Karatayli, Onur Keskin, Mehmet Bektas, Hülya Çetinkaya, Murat Palabiyikoglu, Irfan Soykan, Mithat Bozdayi, Murat Toruner Introduction: R381Q polymorphism of Interleukin 23 Receptor(IL - 23R) gene is associated with Crohn's disease(CD), and Ulcerative Colitis(UC). T300A polymorphism of Authophagy 16 - Like1(ATG16L1) gene is shown to increase the CD risk. There is no previous study on this subject from our country. The purpose of this study is to demonstrate if these polymorphisms have a role in IBD risk, and to determine their effect over clinical parameters. Material and Methods: Among 222 inflammatory bowel disease cases admitted to the Gastroenterology Department, and 134 healthy control cases, the IL23R, and ATG16L1 Polymorphisms were studied by PCR-RFLP. Besides, among a prospective cohort of 130 patients(UC: 67, CD: 63), age of disease onset, duration, involvement sites, activity, treatment (corticosteroid, immune - modulator, biologic) responses, need for surgery, disease type (UC; left sided vs pancolitis, CD; luminal, stenotic, fistulizing), extra - intestinal involvement, hematologic, biochemical parameters were recorded, and correlation to the SNP's were evaluated. Distribution of all the SNP's were found to be according to Hardy - Weinberg Equilibrium (HWE). Results: The frequency of mutation in IL23R gene was 3%, 2%, and 7% respectively in UC, CD, and control group, thus this polymorphism was protective against both UC, and CD development[OR = 0.32(95% Confidence Interval: 0.12 - 0.84), p=0.027; OR = 0.25(95% Confidence Interval: 0.08 - 0.76, p=0.013), respectively](Table 1). The frequency of mutation in ATG16L1 region was 46%, 53 %, and 42% respectively in UC, CD, and control group, thus there was no effect on UC development, but it significantly increased development of CD(p=0.024, Spearman R=0.149). In UC patients there was a female predominance, and higher AST levels correlated with ATG16L1 polymorphism, and increased likelihood of Sero - negative Spondyloarthropathy, and bowel resection IL23R mutation carriers. Among the cases with CD, ATG16L1 polymorphism was related to higher levels of Alkalene Phosphatase, and increased Erythema Nodosum (EN) risk, whereas IL23R was related to increased EN coincidence, and higher disease activity. All these genotype - phenotype correlations should be evaluated cautiously due to low number of cases. There was no other significant phenotype association between UC and CD with SNP's. There is no correlation between corticosteroid, anti - TNF treatment response, need for surgery and polymorphisms. Conclusion: As a result, IL23R polymorphism is protective against development of both UC, and CD in the Turkish population. ATG16L1 is a highly polymorphic gene region, and its polymorphism is a risk factor for development of CD, but has no effect over UC. For both of these mutations, there is no very striking genotype - phenotype interaction. Table 1. Genotypes for the related SNP's among UC, CD, and control cases, and the risk of disease.
Chromatography of DNA sequence of Exon 5 in the SPINT2 gene; control, case and case's mother. Su2074 Genetic Polymorphisms in Serotonin Transporter and G-Protein Genes in Patients With Irritable Bowel Syndrome Zhi-Dong Jiang, Andrew W. Dupont, Herbert L. DuPont, Greg Galler, Francisco J. GarciaTorres, Ned Snyder, Mercedes Paredes, Stephen A. Harold Serotonin is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Polymorphisms in the promoter region of the serotonin transporter gene (5-HTT LPR) have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Furthermore, another gene of interest encodes the β3 subunit of the G-protein (GNβ3) which diminishes G-protein activation. The aim of this study was to assess the potential association between the polymorphisms and the IBS. We compared potential genetic polymorphisms for association with irritable bowel syndrome (IBS), including STin2, HRT3A, HRT3E, Card15 and 3 cytokine genes, IL-8, IL10 and TNF-α. We enrolled 126 subjects with IBS (62 subjects with post-infectious [PI] and 64 subjects with idiopathic [I] forms) and 82 healthy subjects as controls. Subjects with either form of IBS completed a validated questionnaire establishing the diagnosis of IBS by Rome II criteria. The subjects provided blood samples for DNA that was subjected to PCR amplification with primers specific for polymorphisms in the study genes identified by pyrosequencing. There were a significant difference between single nucleotide polymorphisms in 5-HTT LPR, HRT3A C-42T and CNβ3 (C825T) among cases and controls (table). There were no significant differences for the other SNPs studied. This study suggests that there are polymorphism differences in serotonin transporter gene and GNβ3 between patients with IBS and healthy controls seen in a large medical clinic in Houston, Texas. These polymorphisms appear to influence disturbances in gut function in individuals suffering from both PI-IBS and I-IBS.
AGA Abstracts
S-562
AGA Abstracts
Background: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically predisposed individuals. FOXP3 is the master regulator for the development and suppressive function of regulatory T cells, a minor subpopulation of CD4+ T cells Involved in regulation of immune response, maintaining immunological self-tolerance and immune homeostasis, including control of autoimmune diseases and cancer surveillance. Polymorphisms in foxp3 gene have been associated to several autoimmune diseases as autoimmune thyroid disease and systemic lupus erythematosus. The presence of polymorphisms in foxp3 gene could potentially alter the FOXP3 function and therefore potentially related to celiac disease onset. Aim: To detect potential correlation between foxp3 gene polymorphisms and the onset of celiac disease. Methods: DNA previously extracted from 6 celiac and 8 control patients was amplified by PCR. The foxp3 gene was then entirely sequenced and the obtained sequences compared with the foxp3 sequence in GENE BANK. From this screening analysis we were able to select one point mutation that seemed to be potentially associated with celiac disease (rs3761547), a polymorphism already associated with allergic rhinitis. We then proceeded with the specific screening for this polymorphism in 23 controls and 47 celiac patients.Results: The initial screening showed 50% of the celiac patients presenting the polymorphism rs3761547 while none of the controls presented it. These results lead us to screen a larger number of patients and controls for that specific polymorphism. This expanded analysis failed to reveal any difference between celiac patients and controls, with 20% of both controls and celiac patients showing the polymorphism. Conclusions: In this study we performed a screening of the entire foxp3 gene in order to detect polymorphisms potentially associated with the celiac disease onset. Our analysis didn't reveal any association between celiac disease and the presence of polymorphisms excluding a possible association of celiac disease with point mutations in foxp3.
Positive EPCAM immunostaining of intestinal biopsy. Enterocyte tufts are evident.
Su2076 Interleukin 23 Receptor, and ATG16L1 Gene Polymorphisms in Inflammatory Bowel Diseases, and the Association With the Clinical Course Gökhan Kabaçam, Senem C. Karatayli, Onur Keskin, Mehmet Bektas, Hülya Çetinkaya, Murat Palabiyikoglu, Irfan Soykan, Mithat Bozdayi, Murat Toruner Introduction: R381Q polymorphism of Interleukin 23 Receptor(IL - 23R) gene is associated with Crohn's disease(CD), and Ulcerative Colitis(UC). T300A polymorphism of Authophagy 16 - Like1(ATG16L1) gene is shown to increase the CD risk. There is no previous study on this subject from our country. The purpose of this study is to demonstrate if these polymorphisms have a role in IBD risk, and to determine their effect over clinical parameters. Material and Methods: Among 222 inflammatory bowel disease cases admitted to the Gastroenterology Department, and 134 healthy control cases, the IL23R, and ATG16L1 Polymorphisms were studied by PCR-RFLP. Besides, among a prospective cohort of 130 patients(UC: 67, CD: 63), age of disease onset, duration, involvement sites, activity, treatment (corticosteroid, immune - modulator, biologic) responses, need for surgery, disease type (UC; left sided vs pancolitis, CD; luminal, stenotic, fistulizing), extra - intestinal involvement, hematologic, biochemical parameters were recorded, and correlation to the SNP's were evaluated. Distribution of all the SNP's were found to be according to Hardy - Weinberg Equilibrium (HWE). Results: The frequency of mutation in IL23R gene was 3%, 2%, and 7% respectively in UC, CD, and control group, thus this polymorphism was protective against both UC, and CD development[OR = 0.32(95% Confidence Interval: 0.12 - 0.84), p=0.027; OR = 0.25(95% Confidence Interval: 0.08 - 0.76, p=0.013), respectively](Table 1). The frequency of mutation in ATG16L1 region was 46%, 53 %, and 42% respectively in UC, CD, and control group, thus there was no effect on UC development, but it significantly increased development of CD(p=0.024, Spearman R=0.149). In UC patients there was a female predominance, and higher AST levels correlated with ATG16L1 polymorphism, and increased likelihood of Sero - negative Spondyloarthropathy, and bowel resection IL23R mutation carriers. Among the cases with CD, ATG16L1 polymorphism was related to higher levels of Alkalene Phosphatase, and increased Erythema Nodosum (EN) risk, whereas IL23R was related to increased EN coincidence, and higher disease activity. All these genotype - phenotype correlations should be evaluated cautiously due to low number of cases. There was no other significant phenotype association between UC and CD with SNP's. There is no correlation between corticosteroid, anti - TNF treatment response, need for surgery and polymorphisms. Conclusion: As a result, IL23R polymorphism is protective against development of both UC, and CD in the Turkish population. ATG16L1 is a highly polymorphic gene region, and its polymorphism is a risk factor for development of CD, but has no effect over UC. For both of these mutations, there is no very striking genotype - phenotype interaction. Table 1. Genotypes for the related SNP's among UC, CD, and control cases, and the risk of disease.
Chromatography of DNA sequence of Exon 5 in the SPINT2 gene; control, case and case's mother. Su2074 Genetic Polymorphisms in Serotonin Transporter and G-Protein Genes in Patients With Irritable Bowel Syndrome Zhi-Dong Jiang, Andrew W. Dupont, Herbert L. DuPont, Greg Galler, Francisco J. GarciaTorres, Ned Snyder, Mercedes Paredes, Stephen A. Harold Serotonin is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Polymorphisms in the promoter region of the serotonin transporter gene (5-HTT LPR) have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Furthermore, another gene of interest encodes the β3 subunit of the G-protein (GNβ3) which diminishes G-protein activation. The aim of this study was to assess the potential association between the polymorphisms and the IBS. We compared potential genetic polymorphisms for association with irritable bowel syndrome (IBS), including STin2, HRT3A, HRT3E, Card15 and 3 cytokine genes, IL-8, IL10 and TNF-α. We enrolled 126 subjects with IBS (62 subjects with post-infectious [PI] and 64 subjects with idiopathic [I] forms) and 82 healthy subjects as controls. Subjects with either form of IBS completed a validated questionnaire establishing the diagnosis of IBS by Rome II criteria. The subjects provided blood samples for DNA that was subjected to PCR amplification with primers specific for polymorphisms in the study genes identified by pyrosequencing. There were a significant difference between single nucleotide polymorphisms in 5-HTT LPR, HRT3A C-42T and CNβ3 (C825T) among cases and controls (table). There were no significant differences for the other SNPs studied. This study suggests that there are polymorphism differences in serotonin transporter gene and GNβ3 between patients with IBS and healthy controls seen in a large medical clinic in Houston, Texas. These polymorphisms appear to influence disturbances in gut function in individuals suffering from both PI-IBS and I-IBS.
AGA Abstracts
S-562