title: 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.affiliation: Centre for Paediatric and Adolescent Rheumatology, Division of Infection and Immunity, University College London, London, United Kingdom. patricia.woo@ucl.ac.uk
authors.forename: Patricia
authors.initials: P
authors.lastname: Woo
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics; D015870:Gene Expression; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D036281:Genetic Research; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
references.citation: Arthritis Rheum. 2003 Nov;48(11):3202-6
references.pmid: 14613283
references.citation: Pediatr Rheumatol Online J. 2008 Jul 21;6:11
references.pmid: 18644131
references.citation: Genes Immun. 2012 Oct;13(7):583-6
references.pmid: 22895491
references.citation: Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1458-63
references.pmid: 11557672
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: Arthritis Rheum. 2005 Mar;52(3):818-25
references.pmid: 15751095
references.citation: Lancet. 2012 Mar 31;379(9822):1214-24
references.pmid: 22421340
references.citation: Arthritis Res Ther. 2005;7(6):R1281-8
references.pmid: 16277681
references.citation: J Clin Invest. 1998 Oct 1;102(7):1369-76
references.pmid: 9769329
references.citation: PLoS Med. 2005 Aug;2(8):e124
references.pmid: 16060722
references.citation: Lancet. 2005 Dec 3;366(9501):1906-8
references.pmid: 16325682
references.citation: Eur Heart J. 2013 Dec;34(48):3707-16
references.pmid: 23111417
references.citation: Cytokine. 2008 May;42(2):256-264
references.pmid: 18406623
references.citation: N Engl J Med. 2012 Dec 20;367(25):2385-95
references.pmid: 23252525
references.citation: Clin Chem. 2008 May;54(5):841-50
references.pmid: 18356242