Association study of functional genetic variants of innate immunity related genes in celiac disease

B Rueda,Bpc Koeleman,A Zhernakova,J Martín,Ma López-Nevot

doi:10.1186/1471-2350-6-29

Abstract

BackgroundRecent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD) pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition.MethodsWe performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT) that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered.ResultsThe TDT analysis for IL-1α, IL-1β, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed.ConclusionOur results suggest that the analysed polymorphisms of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.

Highlights

Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD) pathogenesis
Genetic variants within regulatory regions that can affect trancription and protein production levels, RANTES -403 G/A and -28 G/C and MCP-1 -2518 G/A single nucleotide polymorphisms (SNPs), were described [22,23,24]. Taking into consideration these findings, in this work we aimed to investigate the possible implication of IL-1α, IL1β, IL-1 receptor agonist (IL-1RN), IL-18, RANTES and MCP-1 functional polymorphisms in CD susceptibility
IL1 gene cluster The transmission pattern for IL-1α -889, IL-1β -511 and IL-1RN VNTR polymorphisms is shown in table 2

Summary

Introduction

Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD) pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. Certain gluten peptides bound to DQ2 or DQ8 molecules cause proliferation and production of proinflammatory cytokines by lamina propria CD4 +T cells [3]. Besides this activation of adaptive immune response, recent evidences suggest that (page number not for citation purposes)

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