Analysis of IL6 and IL1A gene polymorphisms in UK and Dutch patients with sarcoidosis |
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Authors: | Grutters Jan C Sato Hiroe Pantelidis Panagiotis Ruven Henk J T McGrath Deirdre S Wells Athol U van den Bosch Jules M M Welsh Kenneth I du Bois Roland M |
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Affiliation: | Heart Lung Center Utrecht, Department of Pulmonology, Sint Antonius Hospital, Nieuwegein, The Netherlands. j.grutters@antonius.net |
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Abstract: | BACKGROUND: Proinflammatory cytokines are a major determinant in the inflammatory events leading to sarcoidosis. Genetic variations in the genes encoding these cytokines might contribute to sarcoidosis susceptibility, disease severity and outcome. METHODS: In the present study we genotyped two clinically well-defined cohorts of Caucasian sarcoidosis patients from different European countries (each with their own controls) for the following polymorphisms using SSP-PCR: IL6 -174(G/C), IL6 intron 4(A/G) and IL1A-889(C/T). In total, 516 individuals were studied (147 UK + 102 Dutch patients, 101 UK + 166 Dutch controls). Disease severity data at presentation included chest radiographic stage, FVC, DL(CO), and extrapulmonary manifestations. Disease progression was evaluated on follow-up chest radiographs and sequential lung function measurements (2, 4 years). RESULTS: No differences in genotype, carriage and allele frequencies of the investigated polymorphisms were found in either of the populations. Analysis of genotype data in relation to disease severity data, however, showed a slightly increased carrier frequency of the rarer-174C allele in patients with Stage IV sarcoidosis (p = 0.03, Pc = 0.09). Pulmonary function progression analysis did not reveal significant associations. CONCLUSIONS: Although the investigated polymorphisms are unlikely to contribute to sarcoidosis susceptibility, the IL6-174C allele might have a role in the genetics underlying sarcoidosis severity or the progression towards pulmonary fibrosis in a particular subgroup. |
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