The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn's disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy-Weinberg equilibrium was first assessed, and then, the Kruskal-Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients' characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy-Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.

1st Department of Surgery Faculty of Medicine Pavol Jozef Safarik University and Louis Pasteur University Hospital Trieda SNP1 040 11 Kosice Slovakia

Clinica Medica 1 Department of Internal Medicine and Therapeutics 1 R C C S Policlinico San Matteo Foundation and University of Pavia Pavia Italy

Department of Internal Medicine Brothers of Mercy Hospital Polni 3 63900 Brno Czech Republic 2nd Department of Surgery Faculty of Medicine Masaryk University and St Anne's University Hospital Brno Czech Republic

Faculty of Health and Social Work Trnava University Trnava Slovakia

Gastroenterology and Digestive Endoscopy Unit Legnano Hospital ASST Ovest Milanese Legnano Italy

Gastroenterology Unit Department of Medicine AOUI Policlinico G B Rossi and University of Verona Piazzale L A Scuro 10 37134 Verona Italy

Interdipartimental Center for the Molecular Medicine Research and Cardiology Unit Istituto di Cura Città di Pavia and University of Pavia Pavia Italy

Service of Clinical Epidemiology and Biostatistics Fondazione 1 R C C S Policlinico San Matteo Pavia Italy

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