6q23 区域中 TNFAIP3 上游的遗传变异与 HIV/HCV 合并感染患者的肝脏疾病严重程度相关：一项横断面研究。
Genetic variants upstream of TNFAIP3 in the 6q23 region are associated with liver disease severity in HIV/HCV-coinfected patients: A cross-sectional study.
机构信息
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
出版信息
Infect Genet Evol. 2019 Jan;67:112-120. doi: 10.1016/j.meegid.2018.10.008. Epub 2018 Oct 15.
BACKGROUND
TNFAIP3 is a crucial hepatoprotective factor due to its anti-inflammatory, anti-apoptotic, anti-oxidant and pro-regenerative functions. The aim of this study was to analyze the associations between genetic variants upstream of TNFAIP3 (rs675520, rs9376293 and rs6920220) and liver fibrosis severity and inflammation in HIV/HCV-coinfected patients.
METHODS
A cross-sectional study was carried out in 215 HIV/HCV-coinfected patients, who underwent a liver biopsy. TNFAIP3 polymorphisms were genotyped using GoldenGate® assay. Outcome variables were: a) liver fibrosis (Metavir score) [fibrosis stage (F0, F1, F2, F3 and F4) and advanced fibrosis and cirrhosis (F ≥ 3 and F4, respectively)]; b) non-invasive indexes [FIB-4, APRI, and their cut-offs (FIB-4 ≥ 3.25 and APRI≥1.5)]; c) inflammation-related biomarkers (leptin, HGF, NGF, sFasL, sFas, MIF, HA, Ang-2, TIMP1, MMP1 and MMP2).
RESULTS
Patients with rs675520 AG/GG genotypes had decreased odds of having cirrhosis (F4) and advanced fibrosis (FIB-4 ≥ 3.25 and APRI≥1.5) [adjusted Odd Ratio (aOR) = 0.30 (p = 0.025), aOR = 0.20 (p = 0.014), and aOR = 0.34 (p = 0.017), respectively] and lower levels of FIB-4 and APRI [adjusted arithmetic mean ratio (aAMR) = 0.76 (p = 0.003) and aAMR = 0.72 (p = 0.006), respectively]. Patients with rs9376293 CT/CC genotypes had decreased odds of APRI≥1.5 [aOR = 0.39 (p = 0.030)] and lower levels of APRI [aAMR = 0.77 (p = 0.018)]. Patients with rs6920220 AG/AA genotypes had higher odds of having FIB-4 ≥ 3.25 [aOR = 3.72 (p = 0.043)]. Moreover, rs675520 AG/GG genotypes, compared to AA genotype, were associated with lower levels of leptin and NGF (p = 0.002 and p = 0.001, respectively) and higher levels of sFas, MIF, TIMP1 and MMP2 (p = 0.004, p = 0.007, p = 0.020 and p = 0.036, respectively). Also, rs9376293 CT/CC genotypes were related to lower leptin levels (p = 0.026) and higher sFas, MIF, TIMP1 and MMP2 levels (p = 0.029, p = 0.040, p = 0.022 and p = 0.024, respectively).
CONCLUSIONS
Genetic variants upstream of TNFAIP3 were associated with the liver fibrosis severity and inflammation in HIV/HCV-coinfected patients.
背景
TNFAIP3 是一种重要的肝保护因子，具有抗炎、抗凋亡、抗氧化和促进再生的功能。本研究旨在分析 TNFAIP3 上游遗传变异（rs675520、rs9376293 和 rs6920220）与 HIV/HCV 合并感染患者肝纤维化严重程度和炎症之间的关系。
方法
对 215 例 HIV/HCV 合并感染患者进行了一项横断面研究，这些患者接受了肝活检。使用 GoldenGate®assay 对 TNFAIP3 多态性进行基因分型。结果变量为：a）肝纤维化（Metavir 评分）[纤维化分期（F0、F1、F2、F3 和 F4）和进展性纤维化和肝硬化（F≥3 和 F4）]；b）非侵入性指标[FIB-4、APRI 及其截断值（FIB-4≥3.25 和 APRI≥1.5）]；c）炎症相关生物标志物（瘦素、HGF、NGF、sFasL、sFas、MIF、HA、Ang-2、TIMP1、MMP1 和 MMP2）。
结果
与 rs675520 AG/GG 基因型患者相比，rs675520 AG/GG 基因型患者发生肝硬化（F4）和进展性纤维化（FIB-4≥3.25 和 APRI≥1.5）的几率降低[校正优势比（aOR）=0.30（p=0.025）、aOR=0.20（p=0.014）和 aOR=0.34（p=0.017）]，FIB-4 和 APRI 水平也较低[aAMR=0.76（p=0.003）和 aAMR=0.72（p=0.006）]。rs9376293 CT/CC 基因型患者发生 APRI≥1.5 的几率降低[aOR=0.39（p=0.030）]，APRI 水平也较低[aAMR=0.77（p=0.018）]。rs6920220 AG/AA 基因型患者发生 FIB-4≥3.25 的几率增加[aOR=3.72（p=0.043）]。此外，与 AA 基因型相比，rs675520 AG/GG 基因型患者的瘦素和 NGF 水平较低（p=0.002 和 p=0.001），sFas、MIF、TIMP1 和 MMP2 水平较高（p=0.004、p=0.007、p=0.020 和 p=0.036）。此外，rs9376293 CT/CC 基因型与较低的瘦素水平相关（p=0.026）和较高的 sFas、MIF、TIMP1 和 MMP2 水平相关（p=0.029、p=0.040、p=0.022 和 p=0.024）。
结论
TNFAIP3 上游遗传变异与 HIV/HCV 合并感染患者的肝纤维化严重程度和炎症有关。
Zotero 插件