Purpose: Polymorphisms in cytokine genes can determine their level of expression and affect the phenotypic expression of immunomediated diseases, such as celiac disease (CD). We thus evaluated cytokine polymorphism prevalence in CD patients and population controls, and assessed the correlation between specific polymorphisms and celiacs' clinical characteristics.
Methods: 155 CD patients and 202 population controls were enrolled in the study. Cytokine polymorphisms (TNFalpha -308 and -238, IL-1beta -511 and +3954, IL-1b RN + 2018, IL-6 -174, IL-10 -1082, -819 and -592, TGFbeta1 + 29 and +74, IFN-gamma + 874) and HLA class II alleles were determined by sequence-specific primer polymerase chain reaction or restriction fragment length polymorphism analysis. Duodenal histology was classified using Marsh's criteria. Variables significantly associated with CD patients' characteristics were identified by multivariate logistic regression analysis.
Results: A significantly higher frequency of -308 TNFalpha polymorphism was observed in CD patients compared to the entire population control group, although no difference was detected when population controls were stratified according to HLA class II. Among celiacs, early onset of the disease (< or =2 year old) and the presence of a severe intestinal lesion (Marsh 3C) were significantly associated with the -1082 A/A IL-10 genotype which corresponds to a low producer phenotype (OR 3.28, 95% CI 1.49-7.19 and OR 2.60, 95% CI 1.04-6.49, respectively).
Conclusion: The association between IL-10 genotypes and both histological severity at diagnosis and age of onset could be related to an alteration in cytokine balance, and supports the idea that the various clinical manifestations of the disease could be determined by a different genetic background.