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Polymorphic haplotypes of the interleukin‐10 5′ flanking region determine variable interleukin‐10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis

Polymorphic haplotypes of the interleukin‐10 5′ flanking region determine variable interleukin‐10... 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). Conclusion 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arthritis & Rheumatism Wiley

Polymorphic haplotypes of the interleukin‐10 5′ flanking region determine variable interleukin‐10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis

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References (62)

Publisher
Wiley
Copyright
Copyright © 1999 by the American College of Rheumatology
ISSN
0004-3591
eISSN
1529-0131
DOI
10.1002/1529-0131(199906)42:6<1101::AID-ANR6>3.0.CO;2-Y
pmid
10366102
Publisher site
See Article on Publisher Site

Abstract

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). Conclusion 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.

Journal

Arthritis & RheumatismWiley

Published: Jun 1, 1999

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