The− 174G allele of the interleukin‐6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic …
EM Ogilvie, MS Fife, SD Thompson… - Arthritis & …, 2003 - Wiley Online Library
Arthritis & Rheumatism, 2003•Wiley Online Library
Objective Levels of interleukin‐6 (IL‐6) have been shown to correlate with the fever and
disease activity of systemic juvenile idiopathic arthritis (JIA). In a previous case–control
study, a significant association between the IL‐6− 174 nucleotide variant and systemic JIA
was noted, and HeLa cell transfection assays show functional differences in levels of
transcription of the IL‐6− 174 alleles. The present study was undertaken to confirm the
previous findings and to assess possible association with variations of the AnTn tract in the …
disease activity of systemic juvenile idiopathic arthritis (JIA). In a previous case–control
study, a significant association between the IL‐6− 174 nucleotide variant and systemic JIA
was noted, and HeLa cell transfection assays show functional differences in levels of
transcription of the IL‐6− 174 alleles. The present study was undertaken to confirm the
previous findings and to assess possible association with variations of the AnTn tract in the …
Objective
Levels of interleukin‐6 (IL‐6) have been shown to correlate with the fever and disease activity of systemic juvenile idiopathic arthritis (JIA). In a previous case–control study, a significant association between the IL‐6 −174 nucleotide variant and systemic JIA was noted, and HeLa cell transfection assays show functional differences in levels of transcription of the IL‐6 −174 alleles. The present study was undertaken to confirm the previous findings and to assess possible association with variations of the AnTn tract in the promoter.
Methods
We studied a cohort of JIA families from 3 countries, using transmission disequilibrium testing. Genotyping of the −174 nucleotide variant was done by restriction fragment length polymorphism, heteroduplex analysis, or allelic discrimination. The AnTn tract at −392 to −373 was typed using DNA sequencing. Statistical analysis was performed using the programs Transmit and EHplus.
Results
There was a significant excess transmission of the −174G allele in the systemic JIA families (P = 0.041). The excess transmission was only to systemic JIA patients with age at onset >5 years (P = 0.007). No significant association with the other subtypes was found. No AnTn alleles or −174/AnTn haplotypes were significantly associated with systemic JIA.
Conclusion
This study confirms that the IL‐6 –174 nucleotide variant is significantly associated with systemic JIA. The significant excess transmission to patients with age at onset >5 years but not to those with age at onset ≤5 years suggests that there may be genetic heterogeneity between the 2 groups.
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