Silva Paula Carolina Valença, Gomes Adriana Vieira, de Britto Lidiane Régia Pereira Braga, de Lima Elker Lene Santos, da Silva Jamile Luciana, Montenegro Silvia Maria Lucena, Muniz Maria Tereza Cartaxo, Domingues Ana Lúcia Coutinho
1 Departamento de Enfermagem, Universidade Federal de Pernambuco (UFPE) , Vitória de Santo Antão, Pernambuco, Brazil .
2 Laboratório de Biologia Molecular, Centro de Oncohematologia Pediátrica, Hospital Universitário Oswaldo Cruz , Universidade de Pernambuco, Recife, Pernambuco, Brazil .
Genet Test Mol Biomarkers. 2017 Nov;21(11):658-662. doi: 10.1089/gtmb.2017.0133. Epub 2017 Oct 31.
The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is an essential component in the host immune response to infection, and it has been reported to be an important mediator in severe periportal fibrosis (PPF). We hypothesized that the (-G308A) polymorphism of the TNF-α gene is associated with the severity of PPF and that these polymorphisms influence TNF-α expression.
In this cross-sectional study, we genotyped these polymorphisms within the TNF-α gene in 256 Brazilian subjects infected with Schistosoma mansoni, with different patterns of PPF.
The genotype (-308) AA was associated with a significant increase in the risk to advanced PPF (OR = 4.60; p = 0.009). In addition, median levels of TNF-α were higher in patients with moderate to advanced PPF, compared with mild fibrosis (20 and 17.3 pg/mL, respectively; p = 0.040). There was no association between average serum levels of TNF-α and (-G308A) TNF-α polymorphism.
Our results suggest the (-308) AA genotype may be a risk factor for severity in advanced PPF, in this Brazilian population, and could potentially be used to predict the severity of advanced PPF in schistosomiasis.
促炎细胞因子肿瘤坏死因子-α(TNF-α)是宿主对感染免疫反应的重要组成部分,据报道它是严重门静脉周围纤维化(PPF)的重要介质。我们推测TNF-α基因的(-G308A)多态性与PPF的严重程度相关,且这些多态性会影响TNF-α的表达。
在这项横断面研究中,我们对256名感染曼氏血吸虫且具有不同PPF模式的巴西受试者的TNF-α基因内的这些多态性进行了基因分型。
基因型(-308)AA与晚期PPF风险显著增加相关(比值比=4.60;p=0.009)。此外,与轻度纤维化患者相比,中度至重度PPF患者的TNF-α中位数水平更高(分别为20和17.3 pg/mL;p=0.040)。TNF-α的平均血清水平与(-G308A)TNF-α多态性之间无关联。
我们的结果表明,在这个巴西人群中,(-308)AA基因型可能是晚期PPF严重程度的一个风险因素,并可能用于预测血吸虫病中晚期PPF的严重程度。