Cooperative Influence of Genetic Polymorphisms on Interleukin 6 Transcriptional Regulation*
By C. Terry, V. Loukaci, F. Green. Journal of Biological Chemistry, 2000
843 citations recorded by the source corpus.
Interleukin 6 (IL6) plays key roles in hematopoiesis, immune, and acute phase responses. Dysregulated IL6 expression is implicated in diseases such as atherosclerosis and arthritis. We have examined the functional effect of four polymorphisms in the IL6 promoter (−597G→A, −572G→C, −373AnTn, −174G→C) by identifying the naturally occurring haplotypes and comparing their effects on reporter gene expression. The results indicate different transcriptional regulation in the ECV304 cell line compared with the HeLa cell line, suggesting cell type-specific regulation of IL6 expression. The haplotypes showed functional differences in the ECV304 cell line; transcription was higher from the GG9/11G haplotype and lower from the AG8/12G allele. The differences suggest that more than one of the polymorphic sites is functional; the base differences at distinct polymorphic sites do not act independently of one another, and one polymorphism influences the functional effect of variation at other polymorphic sites. These results show that genetic polymorphisms in the promoter influence IL6 transcription not by a simple additive mechanism but rather through complex interactions determined by the haplotype.
Subfields: Cancer Research, Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/2b8cc3d0b0bc8aafc5d4dcc9ff6b978223eb8871
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Citations in the corpus
- The anti-inflammatory effect of exercise. (2005, background): “Four polymorphisms exist in the IL-6 promoter, although most population-based studies focus on the G-174-C, where the C allele shows lower IL-6 expression than the G allele (141).”
- Evolutionary Causes and Consequences of Immunopathology (2005, background): “Variation in TNF-α responsiveness—and, more generally, the magnitude of infection-induced inflammatory responses (Terry et al. 2000, van de Vosse et al. 2004)—has a polymorphic genetic basis.”
- Insulin resistance and chronic cardiovascular inflammatory syndrome. (2003, neutral): “Again, divergent results have been described in other populations (224) in keeping with the observation that IL-6 promoter haplotypes (rather than simply single variant sites) influence IL-6 gene expression in vitro (225).”