IL-6 polymorphisms: a useful genetic tool for inflammation research?
Patricia Woo, Steve E. Humphries
Patricia Woo, Steve E. Humphries
Published April 1, 2013
Citation Information: J Clin Invest. 2013;123(4):1413-1414. https://doi.org/10.1172/JCI67221.
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Hindsight

IL-6 polymorphisms: a useful genetic tool for inflammation research?

Abstract

In 1998, we described a novel polymorphism in the promoter (G>C, rs1800795) of the IL-6 (IL6) gene. The common allele, G, exhibited higher transcriptional activity in gene reporter assays and was associated with higher serum IL-6 levels in a small cohort of healthy subjects. We explored the ethnic distribution of these alleles and found significant differences among people of mixed European descent, Africans, and Gujarati Asians. Disease association was established in a cohort of 92 children of mixed European descent from the United Kingdom with systemic juvenile idiopathic arthritis (sJIA), with the GG genotype being significantly increased in sJIA cases compared with that in 383 controls, especially in those under 6 years old (P = 0.01). This polymorphism has since been used as a functional variant to explore the role of elevated IL-6 levels in many common disease states, confirming the key causal role of IL-6 in human health and disease.

Authors

Patricia Woo, Steve E. Humphries

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Figure 1

Mechanism of action of tocilizumab.

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Mechanism of action of tocilizumab. (A) IL-6 triggers the dimerization o...
(A) IL-6 triggers the dimerization of gp130 through binding of IL-6R. (B) Tocilizumab binds to the IL-6R or the soluble IL-6R (sIL-6R), which mediates IL-6 trans-signaling, preventing the binding of IL-6. Loss of IL-6 binding reduces both classical and trans-signaling and reduces activation of the JAK/STAT system, leading to damping of inflammation locally and systemically.