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  • Title: Reduced transcriptional activity in individuals with IL-18 gene variants detected from functional but not association study.
    Author: Liang XH, Cheung W, Heng CK, Wang DY.
    Journal: Biochem Biophys Res Commun; 2005 Dec 16; 338(2):736-41. PubMed ID: 16243298.
    Abstract:
    Genetic polymorphisms of IL-18 and its receptor were reported to be associated with elevated serum IgE levels, atopy, and/or asthma. However, conflicting results were observed in various association studies and functional activity of these polymorphisms remains unclear. A total of 393 unrelated subjects were involved in this study. Direct PCR-sequencing method was used to screen novel polymorphisms. The functional significance of these polymorphisms was investigated using reporter gene assay. Three known (-137, +113, and +127) polymorphisms in the IL-18 promoter were identified with a perfect linkage disequilibrium (Delta=1, p<0.001) among them. No significant difference in the genotype frequencies of these polymorphisms between atopy and atopic phenotypes in Singaporean Chinese, Malays, and Indians was observed. However, transcriptional activities were significantly increased in HepG2 cultured cells with wild-type IL-18 genotype (-137/G, +113/T, and +127/C) than mutated genotype (-137/C, +113/G, and +127/T). Although these polymorphisms appear to have no association with atopic phenotypes in our population, subsequent functional studies suggest that polymorphisms in the IL-18 promoter region could affect significantly its activity.
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