Hahn Eriza Cristina, Zambra Francis Maria Báo, Kamada Anselmo Jiro, Delongui Francieli, Grion Cíntia Magalhães Carvalho, Reiche Edna Maria Vissoci, Chies José Artur Bogo
Department of Genetics, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Department of Genetics, Universidade Federal de Pernambuco - UFPE, Recife, PE, Brazil.
Hum Immunol. 2017 Nov;78(11-12):718-723. doi: 10.1016/j.humimm.2017.09.002. Epub 2017 Sep 21.
The human leukocyte antigen G (HLA-G) is a molecule involved in immune system modulation, acting in the maintenance of a state of immune tolerance. Some polymorphisms in the HLA-G gene 3' untranslated region (3'UTR) were associated to distinct levels of HLA-G expression and to sepsis development. In the present study, haplotypes and polymorphisms of the HLA-G 3'UTR were analyzed in Brazilian septic patients.
The HLA-G 3'UTR was amplified by PCR, sequenced and eight polymorphisms were genotyped (the 14bp insertion/deletion, +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and+3196C/G) in DNA samples from septic patients (with severe sepsis or septic shock) and controls. The haplotypes were inferred and association tests were performed through Chi square test and binary logistic regression.
The+3027AC genotype was associated asa risk factor to sepsis development (OR 3.17, P 0.048). Further, the presence of the UTR-7 haplotype (OR 2.97, P 0.018), and of 14bp-Ins_+3142G_+3187A haplotype (OR 2.39, P 0.045) were associated with sepsis, conferring susceptibility.
Our data confirm an important role of HLA-G 3'UTR polymorphisms in the development of severe forms of sepsis (severe sepsis and septic shock). The genotyping of HLA-G genetic variants and haplotypes could be useful as a prediction tool of increased risk to severe sepsis.
人类白细胞抗原G(HLA - G)是一种参与免疫系统调节的分子,在维持免疫耐受状态中发挥作用。HLA - G基因3'非翻译区(3'UTR)的一些多态性与HLA - G表达的不同水平以及脓毒症的发生有关。在本研究中,对巴西脓毒症患者的HLA - G 3'UTR单倍型和多态性进行了分析。
通过聚合酶链反应(PCR)扩增HLA - G 3'UTR,进行测序,并对脓毒症患者(患有严重脓毒症或脓毒性休克)和对照组的DNA样本中的8种多态性进行基因分型(14bp插入/缺失、+3003T/C、+3010C/G、+3027A/C、+3035C/T、+3142G/C、+3187A/G和+3196C/G)。推断单倍型,并通过卡方检验和二元逻辑回归进行关联测试。
+3027AC基因型作为脓毒症发生的危险因素(比值比3.17,P = 0.048)。此外,UTR - 7单倍型(比值比2.97,P = 0.018)和14bp - Ins_+3142G_+3187A单倍型(比值比2.39,P = 0.045)的存在与脓毒症相关,具有易感性。
我们的数据证实了HLA - G 3'UTR多态性在严重脓毒症(严重脓毒症和脓毒性休克)发生中的重要作用。HLA - G基因变异和单倍型的基因分型可作为严重脓毒症风险增加的预测工具。