Department of Biochemistry, 710 Cumberland Street, University of Otago, Dunedin 9054, New Zealand.
Arthritis Res Ther. 2010;12(3):R116. doi: 10.1186/ar3053. Epub 2010 Jun 16.
The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus.
A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA.
No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR)=0.95 (0.80 to 1.12), P=0.54), or rs17388568 (OR=1.03 (0.90 to 1.19), P=0.65) or rs907715 (OR=0.98 (0.86 to 1.12), P=0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR=0.86 (0.82 to 0.91), P=8.8x10(-8), P=2.1x10(-8) including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR=1.03, (0.98 to 1.09); P=0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR=0.93 (0.87 to 1.00), P=0.07). However, this trend was not independent of the association at rs6822844.
The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P<or=5x10(-8)) level of support for association with RA. As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association.
单核苷酸多态性（SNP）rs6822844 位于 KIAA1109-TENR-IL2-IL21 基因簇内，与类风湿关节炎（RA）有关。该簇内的其他变体，包括与 rs6822844 不连锁不平衡（LD）的 rs17388568，以及与 rs6822844 和 rs17388568 中度 LD 的 rs907715，与多种自身免疫表型有关，包括 1 型糖尿病（T1D）。在这里，我们旨在：一、在全基因组水平上确认 rs6822844 与 RA 的关联，二、评估在 KIAA1109-TENR-IL2-IL21 基因座上是否存在与 rs6822844 无关的 RA 效应。
共对 842 名澳大拉西亚 RA 患者和 1115 名欧洲白种人对照组进行了 rs6822844、rs17388568 和 rs907715 的基因分型。使用 STATA 对这些数据与已发表和公开可用的数据进行了荟萃分析。
在澳大拉西亚样本集中，rs6822844（比值比（OR）=0.95（0.80 至 1.12），P=0.54）或 rs17388568（OR=1.03（0.90 至 1.19），P=0.65）或 rs907715（OR=0.98（0.86 至 1.12），P=0.69）均未观察到统计学意义上的关联。当使用总共 9772 例病例和 10909 例对照的数据进行荟萃分析时，rs6822844 与 RA 具有全基因组水平的显著关联（OR=0.86（0.82 至 0.91），P=8.8x10（-8），P=2.1x10（-8）包括北美类风湿关节炎联盟数据）。使用总共 6585 例病例和 7528 例对照的 rs17388568 荟萃分析显示与 RA 无显著关联（OR=1.03（0.98 至 1.09）；P=0.22），使用总共 2689 例病例和 4045 例对照的 rs907715 荟萃分析显示有相关性的趋势（OR=0.93（0.87 至 1.00），P=0.07）。然而，这种趋势与 rs6822844 的关联并不独立。
KIAA1109-TENR-IL2-IL21 基因簇，编码一种在 Th17 细胞生物学中起重要作用的白细胞介素（IL-21），是第 20 个与 RA 具有全基因组（P<or=5x10（-8））水平关联的基因座。与大多数其他自身免疫性疾病一样，除了 1 型糖尿病（T1D）外，rs6822844 是该基因座的主要关联。KIAA1109-TENR-IL2-IL21 基因座也易患其他自身免疫表型，具有异质的关联模式。
