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NGF (−198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon
Molecular Medicine ( IF 5.7 ) Pub Date : 2020-01-29 , DOI: 10.1186/s10020-019-0134-x
Leonn Mendes Soares Pereira 1, 2 , Ednelza da Silva Graça Amoras 1 , Simone Regina Souza da Silva Conde 3 , Sâmia Demachki 3 , Eduardo José Melo Dos Santos 2, 4 , Sandra Souza Lima 1 , Ricardo Ishak 1, 2 , Antonio Carlos Rosário Vallinoto 1, 2
Affiliation  

Backgrounds Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR 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 p75NTR 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 p75NTR 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 p75NTR (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.

中文翻译:

NGF (−198C > T, Ala35Val) 和 p75NTR (Ser205Leu) 基因突变与巴西亚马逊地区慢性病毒性肝炎患者不同组织病理学特征中的肝功能相关

背景 神经生长因子 (NGF) 是一种神经营养因子,可与 p75NTR 受体相互作用并引发决定细胞存活或死亡的级联反应,两者都与肝组织的生理机能有关。NGF 和 p75NTR 基因中的单核苷酸多态性 (SNP) 已在不同的病理学中进行了研究;然而,没有研究分析它们在肝脏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 S​​NP 对巴西亚马逊地区慢性病毒性肝病患者在炎症和纤维化不同阶段维持肝功能的影响。方法 SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala 和 Ser205Leu 在来自慢性病毒性肝炎患者的样本中通过实时 PCR 进行基因分型,这些患者按炎症和肝纤维化阶段进行分层。从更新的医疗记录中获得组织病理学、病毒载量 (VL)、肝酶和合并症数据。应用流行病学调查问卷强调了其他方面。结果 NGF 中的 -198C/T 和 Ala35Val 多态性与组织病理学特征、VL 和肝酶的变化有关。p75NTR 中的 Ser205Leu 多态性仅与 VL 和肝酶的变化有关。不同种族人群的多态频率是可变的,主要是生物学相关的多态性。已经建立了基于遗传、病毒学、行为和生化方面的多因素相互作用网络。
更新日期:2020-01-29
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