Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Stopford Building, Manchester M13 9PT, UK.
Ann Rheum Dis. 2011 Mar;70(3):463-8. doi: 10.1136/ard.2010.137174. Epub 2010 Nov 10.
Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases.
To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls.
3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test.
The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10(-7)) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10(-8)). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole.
The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE.
有证据表明，类风湿关节炎（RA）和系统性红斑狼疮（SLE）可能存在共同的疾病易感性基因位点。
在英国 RA 患者队列和对照中，调查已报道与 SLE 相关的单核苷酸多态性。
研究纳入了 3962 名 RA 患者和 9275 名对照。研究调查了 11 个位于 SLE 确认基因座的 SNP。这些 SNP 映射到 TNFSF4、BANK1、TNIP1、PTTG1、UHRF1BP1、ATG5、JAZF1、BLK、KIAA1542、ITGAM 和 UBE2L3 基因座。采用趋势检验比较 RA 患者和对照的基因型频率。
BLK 和 UBE2L3 基因座的 SNP 与 RA 具有显著的关联证据。另外两个 SNP，ATG5 和 KIAA1542，与 RA 具有名义上的关联证据（p=0.02 和 p=0.02），但在应用 Bonferroni 校正后并不显著。此外，与对照相比，RA 患者携带 SLE 等位基因的整体富集程度更高（p=9.1×10(-7)）。对这一研究和之前研究的荟萃分析证实了 BLK 和 UBE2L3 基因与 RA 的关联在全基因组显著水平（p<5×10(-8)）。作者估计，迄今为止确定的 SLE 和 RA 重叠基因座（不包括 HLA-DRB1 等位基因），总共解释了 RA 整体遗传易感性的约 5.8%。
这些发现证实了 BLK 和 UBE2L3 基因座与 RA 的关联，从而增加了 RA 和 SLE 之间存在重叠的基因座列表。
