Catamo E, Addobbati C, Segat L, Sotero Fragoso T, Tavares Dantas A, de Ataide Mariz H, Ferreira da Rocha Junior L, Branco PintoDuarte A L, Coelho A V C, de Moura R R, Polesello V, Crovella S, Sandrin Garcia P
University of Trieste, Trieste, Italy.
Tissue Antigens. 2015 Jun;85(6):458-65. doi: 10.1111/tan.12545. Epub 2015 Mar 11.
This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5' upstream regulatory region (URR), 3' untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12% in SLE patients vs 6% in controls; odds ratio (OR), 2.10, 95% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8% in SLE patients and 6.3% in controls; OR, 2.14, 95% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is far from being elucidated yet, our association study results along with a systematic review and meta-analysis suggest that HLA-G might be able to slightly modulate the complex SLE phenotype (pooled OR, 1.14, 95% CI, 1.02-1.27, P = 0.021).
本研究旨在全面分析人类白细胞抗原(HLA)-G多态性与系统性红斑狼疮(SLE)发病易感性及临床表现之间的关联。对来自巴西东北部的114例SLE患者和128例健康对照者的HLA-G 5'上游调控区(URR)、3'非翻译区(UTR)以及外显子3的胞嘧啶缺失(ΔC,HLA-G*0105N等位基因)进行了分析。SLE患者中+3003T>C(rs1707)C等位基因和HG010101c扩展HLA-G等位基因的频率显著高于健康对照者(+3003C等位基因频率:SLE患者为12%,对照者为6%;优势比(OR)为2.10,95%置信区间(CI)为1.06 - 4.28,P = 0.026;HG010101c频率:SLE患者为11.8%,对照者为6.3%;OR为2.14,95%CI为1.01 - 4.51,P = 0.046),且与疾病发生易感性相关。其他多态性与不同的临床表现相关。尽管HLA-G在SLE疾病中的作用尚未完全阐明,但我们的关联研究结果以及一项系统评价和荟萃分析表明,HLA-G可能能够轻微调节复杂的SLE表型(合并OR为1.14,95%CI为1.02 - 1.27,P = 0.021)。