University of Chicago, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, 924 East 57th Street, R420, Chicago, IL 60637, USA.
J Rheumatol. 2012 Jan;39(1):73-8. doi: 10.3899/jrheum.110590. Epub 2011 Nov 1.
UBE2L3 is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis in European ancestry populations, and this locus has not been investigated fully in non-European populations. We studied the UBE2L3 risk allele for association with SLE, interferon-α (IFN-α), and autoantibodies in a predominantly African American SLE cohort.
We studied 395 patients with SLE and 344 controls. The UBE2L3 rs5754217 polymorphism was genotyped using Taqman primer-probe sets, and IFN-α was measured using a reporter cell assay.
The UBE2L3 rs5754217 T allele was strongly enriched in African American patients with anti-La antibodies as compared to controls, and a recessive model was the best fit for this association (OR 2.55, p = 0.0061). Serum IFN-α also demonstrated a recessive association with the rs5754217 genotype in African American patients, and the TT/anti-La-positive patients formed a significantly high IFN-α subgroup (p = 0.0040). Similar nonstatistically significant patterns of association were observed in the European American patients with SLE. Case-control analysis did not show large allele frequency differences, supporting the idea that this allele is most strongly associated with anti-La-positive patients.
This pattern of recessive influence within a subgroup of patients may explain why this allele does not produce a strong signal in standard case-control studies, and subphenotypes should be included in future studies of UBE2L3. The interaction we observed between UBE2L3 genotype and autoantibodies upon serum IFN-α suggests a biological role for this locus in patients with SLE in vivo.
UBE2L3 与欧洲血统人群的系统性红斑狼疮（SLE）和类风湿关节炎易感性相关，而该基因座在非欧洲人群中尚未得到充分研究。我们研究了UBE2L3 风险等位基因与 SLE、干扰素-α（IFN-α）和主要为非裔美国人的 SLE 队列中的自身抗体的关联。
我们研究了 395 例 SLE 患者和 344 例对照。UBE2L3 rs5754217 多态性使用 Taqman 引物-探针组进行基因分型，IFN-α 使用报告细胞测定法进行测量。
与对照相比，UBE2L3 rs5754217 T 等位基因在具有抗 La 抗体的非裔美国 SLE 患者中明显富集，而隐性模型最适合这种关联（OR 2.55，p = 0.0061）。血清 IFN-α 也显示与 rs5754217 基因型在非裔美国患者中呈隐性关联，并且 TT/抗 La 阳性患者形成了一个明显高 IFN-α亚组（p = 0.0040）。在 SLE 的欧洲裔美国患者中也观察到类似的非显著关联模式。病例对照分析并未显示大等位基因频率差异，支持该等位基因与抗 La 阳性患者最密切相关的观点。
这种在亚组患者中隐性影响的模式可能解释了为什么该等位基因在标准病例对照研究中不会产生强烈信号，并且在未来的 UBE2L3 研究中应包括亚表型。我们观察到的 UBE2L3 基因型与血清 IFN-α 之间的自身抗体相互作用提示该基因座在体内 SLE 患者中具有生物学作用。
