Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis.
OBJECTIVE
To determine the distribution of the interleukin-10 (IL-10) 5' flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype.


METHODS
Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype.


RESULTS
Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P = 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02).


CONCLUSIONS
The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.
Crawley
E
E
University College , London Medical School, UK.
Kay
R
R
Sillibourne
J
J
Patel
P
P
Hutchinson
I
I
Woo
P
P
D001171:Arthritis, Juvenile / Q000097:blood / Q000150:complications / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005128:Eye Diseases / Q000097:blood / Q000150:complications / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D020298:U937 Cells / Q000378:metabolism
D017931:DNA Primers; D016753:Interleukin-10