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巴西系统性红斑狼疮患者 HLA - G 5'上游调控区和 3'非翻译区多态性的综合分析

Comprehensive analysis of polymorphisms in the HLA-G 5' upstream regulatory and 3' untranslated regions in Brazilian patients with systemic lupus erythematosus.

作者信息

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

机构信息

University of Trieste, Trieste, Italy.

出版信息

Tissue Antigens. 2015 Jun;85(6):458-65. doi: 10.1111/tan.12545. Epub 2015 Mar 11.

DOI:10.1111/tan.12545
PMID:25762019
Abstract

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).

摘要

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)。

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