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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.