神经生长因子（-198C>T，Ala35Val）和 p75（Ser205Leu）基因突变与巴西亚马逊地区慢性病毒性肝炎不同组织病理学特征患者的肝功能有关。
NGF (-198C > T, Ala35Val) and p75 (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon.
机构信息
Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.
Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.
出版信息
Mol Med. 2020 Jan 29;26(1):12. doi: 10.1186/s10020-019-0134-x.
BACKGROUNDS
Neural growth factor (NGF) is a neurotrophin that can interact with the p75 receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75 genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon.
METHODS
The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires.
RESULTS
The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75 was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects.
CONCLUSION
Mutations in the NGF (-198C > T, Ala35Val) and p75 (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.
背景
神经生长因子（NGF）是一种神经营养因子，可与 p75 受体相互作用，引发一系列反应，决定细胞的存活或死亡，而这两者都与肝组织的生理学有关。NGF 和 p75 基因中的单核苷酸多态性（SNPs）已在不同的病理中进行了研究；然而，目前尚无研究分析它们在肝微环境中的生物学作用。在本研究中，我们评估了这些基因中的 SNP 对巴西亚马逊地区慢性病毒性肝病患者炎症和纤维化不同阶段肝功能维持的影响。
方法
通过实时 PCR 对慢性病毒性肝炎患者按炎症和纤维化阶段分层的样本进行 -198C>T、Arg80Gln、Val72Met、Ala35Val、Ala18Ala 和 Ser205Leu 基因的 SNP 分型。从更新的病历中获取组织病理学、病毒载量（VL）、肝酶和合并症数据。通过应用流行病学问卷突出了其他方面。
结果
NGF 的 -198C/T 和 Ala35Val 多态性与组织病理学特征、VL 和肝酶的变化有关。p75 的 Ser205Leu 多态性仅与 VL 和肝酶的变化有关。多态性频率在不同的种族群体中有所不同，主要是与生物学相关的多态性。基于遗传、病毒学、行为和生化方面，建立了一个多因素相互作用的网络。
结论
NGF（-198C>T、Ala35Val）和 p75（Ser205Leu）基因中的突变，在多因素方面的列表中，与巴西亚马逊地区慢性病毒性肝病患者不同组织病理学特征的肝功能有关。
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