Novel IL-6 haplotypes and disease association.
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.
Fife
M S
MS
Pediatric and Adolescent Rheumatology, University College London, UK. m.fife@ucl.ac.uk
Ogilvie
E M
EM
Kelberman
D
D
Samuel
J
J
Gutierrez
A
A
Humphries
S E
SE
Woo
P
P
D001171:Arthritis, Juvenile / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D015850:Interleukin-6