1. ¹Pediatric and Adolescent Rheumatology, University College London, UK
2. ²British Heart Foundation Laboratories, Centre for Cardiovascular Genetics, Department of Medicine, University College London, UK

Correspondence: Dr MS Fife, Department of Immunology and Molecular Pathology, University College London, 46 Cleveland St., London W1T 4JF, UK. E-mail: m.fife@ucl.ac.uk

Received 1 December 2004; Revised 11 February 2005; Accepted 16 February 2005; Published online 7 April 2005.

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine crucial in both adaptive and innate immunity. Numerous genetic studies have shown association with variants of this gene in a multitude of diseases and phenotypes. Most tests of association have focused on a limited set of promoter polymorphisms, in particular, the -174G>C; however, there are many inconsistencies within and between these studies. We propose that there is a more complex regulatory haplotype extending further upstream of the previously characterised promoter region which will provide a more detailed view of the effect of variation on lL-6 regulation. We have exploited two additional single nucleotide polymorphisms (SNPs) in IL-6 that, when examined as a haplotype with existing markers, show an increased level of association with systemic onset juvenile arthritis in a family-based study. This suggests that the haplotype effect may be more functionally relevant to the disease.