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P363. The IL-10 promoter polymorphisms is associated with both CD and UC in Tuscany population

A.L. Putignano1, S. Genise2, S. Bagnoli2, M. Milla2, A. Tedde3, D. Molinaro4, R. Sestini4, M. Genuardi1, V. Annese2, L. Papi4

1Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Fiorgen Farmacogenomic Foundation, Sesto Fiorentino, Florence, Italy; 2Gastroenterology Unit, University Hospital Careggi, Florence, Florence, Italy; 3Neurogenetic Unit, Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy; 4Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy

Background: Crohn's disease (CD) and ulcerative colitis (UC) are relatively common chronic intestinal inflammatory disorders characterized by a dysregulated mucosal immune response in genetically susceptible host. They are considered complex genetic disorders, with multiple contributing genes interacting with environmental factors. A number of genome wide association and replication studies have demonstrated the involvement of cytokine-related genes.

Materials and Methods: In this project we analyzed two SNPs of IL-10 promoter, −1082G>A (rs1800896) and-819C>T (rs1800871), known to reduce the production of the anti-inflammatory IL-10 cytokine, in 554 patients (315 UC and 238 CD) and 367 healthy controls from Tuscany, Italy. Genotyping was conducted by PCR-HRM and direct sequencing analysis. Statistical analysis was performed using EpiInfo software (URL: www.cdc.gov/EpiInfo/) to assess the risk between the genotypic groups. Haplotype frequencies were calculated using PowerMarker software, version 3.25 (http://statgen.ncsu.edu/powermarker/).

Results: The −1082G>A (rs1800896) SNP followed the Hardy-Weinberg equilibrium in both UC and CD patients and controls. The HW equilibrium for the −819 C/T (rs1800871) SNP was, however, respected only in the control group (p = 0.58) and not in the UC (p = 0.006) and CD (p = 0.0001) cases. This may be further evidence of the association of the locus with the disease.

The frequency of the IL10-1082A allele was significantly higher both in UC (OR = 2.33, CI = 1.65–3.29, p < 0.0001) and in CD patients (OR = 1.44, CI = 1.13–1.83, p = 0.0023) than in controls. The IL10-819T allele was weakly associated in UC patients (OR = 1.28, CI = 1.0–1.64, p = 0.046), and more significantly also with CD patients (OR = 2.14, CI = 1.66–2.77, p < 0.0001), compared to controls. In addition, we demonstrated an higher frequency of A/T haplotype of IL-10 gene in both UC (OR = 7.54, CI = 3.26–18.1, p < 0.0001) and CD patients (OR = 17.1, CI = 7.6–40, p < 0.0001), compared to controls.

We found that rs1800896 SNP was in low LD with rs1800871 both in CU and CD cases (r2 = 0.08) and controls (r2 = 0.12).

Conclusion: We have demonstrated a positive association of investigated SNPs of IL-10 promoter and A/T haplotye which might influence IL-10 production, thus corroborating potential therapeutic implications.