Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P
University College , London Medical School, UK.
Arthritis Rheum. 1999 Jun;42(6):1101-8. doi: 10.1002/1529-0131(199906)42:6<1101::AID-ANR6>3.0.CO;2-Y.
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.
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.
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).
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.
确定白细胞介素-10（IL-10）5'侧翼区单倍型在关节炎患儿及对照组中的分布，并研究各单倍型的功能意义。
采用序列特异性寡核苷酸探针法确定单倍型频率。通过瞬时转染研究来探究各单倍型驱动的报告基因的转录情况。进行全血培养以评估各基因型的IL-10产生情况。
累及超过4个关节的关节炎患者比关节炎局限于少于4个关节的患者更有可能具有ATA单倍型的基因型。该ATA单倍型与比GCC单倍型更低的转录活性相关（P = 0.02），并且ATA/ATA基因型在脂多糖刺激下与比其他基因型更低的IL-10产生相关（P < 0.02）。
本研究结果证明了ATA单倍型的功能意义，并揭示了包含该单倍型的基因型与扩展性寡关节炎之间的显著关联。
