Previously, an association between susceptibility to sarcoidosis and a polymorphism in the interleukin (IL-18) gene (IL-18 -607A/C) has been reported in Japanese. The aim of the present study was to validate this association in a clinically well-characterized population of Dutch Caucasians. Three other polymorphisms at positions -656, -137, and 1248 were included in order to extend the mapping of the IL-18 gene and to enable the construction of haplotypes. Polymorphisms were determined using sequence-specific primers (SSPs) and polymerase chain reaction (PCR). A total of 236 individuals was studied (133 patients and 103 controls). No significant differences were observed in the distribution of the -607 and the other polymorphisms between Dutch sarcoidosis patients and controls. However, significant differences in IL-18 -607 genotype and allele frequency distributions were found between the Dutch and the Japanese. From the investigated IL-18-promoter polymorphisms, we were able to deduce four haplotypes. No differences were observed in haplotype frequencies between Dutch sarcoidosis patients and controls. In conclusion, IL-18 polymorphisms do not appear to influence the susceptibility to sarcoidosis in Dutch Caucasians. Important differences in allele frequencies were observed between Japanese and Dutch sarcoidosis patients and controls.
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