Toll样受体8（TLR8）基因多态性与HIV/HCV合并感染患者慢性丙型肝炎的病情无进展相关。
Toll-like receptor 8 (TLR8) polymorphisms are associated with non-progression of chronic hepatitis C in HIV/HCV coinfected patients.
作者信息
Fernández-Rodríguez Amanda, Berenguer Juan, Jiménez-Sousa María A, García-Álvarez Mónica, Aldámiz-Echevarría Teresa, Pineda-Tenor Daniel, Diez Cristina, de la Barrera Jorge, Bellon Jose Mª, Briz Verónica, Resino Salvador
机构信息
Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
出版信息
Infect Genet Evol. 2015 Dec;36:339-344. doi: 10.1016/j.meegid.2015.10.006. Epub 2015 Oct 9.
Toll-like receptor 8 (TLR8) polymorphisms have been related to hepatitis C virus (HCV) infection. The aim was to estimate the association of TLR8 polymorphisms with HCV-related outcomes in HIV/HCV coinfected patients. We performed a cross-sectional study of 220 patients who underwent a liver biopsy. TLR8 polymorphisms were genotyped using GoldenGate® assay. The outcome variables were non-fibrosis (F0), mild-inflammation (A0/A1), and non-steatosis [fatty hepatocytes (FH) <10%]. Logistic regression analysis was used to compare the outcome variables according to TLR8 polymorphisms. Four polymorphisms were analyzed (rs1013151, rs5744069, rs17256081 and rs3764880rs1013151). Female patients had higher frequency of TLR8 major alleles at rs17256081 and rs101315, and minor alleles at rs3764880 and rs5744069. Male patients had higher frequency of TLR8 minor alleles except for rs3764880, where major alleles were higher (p<0.01). Two TLR8 polymorphisms (rs1013151 and rs5744069) were significantly associated with non-fibrosis (F0) [adjusted odds ratio (aOR)=4.42 (95% of confidence interval (95%CI)=1.54; 12.68) (p=0.006) and aOR=4.76 (95%CI=1.69; 13.37) (p=0.003); respectively]. When data were stratified by gender, rs1013151 and rs5744069 polymorphisms remained significant for male patients [adjusted odds ratio (aOR)=4.49 (95%CI=1.08; 18.62) (p=0.039) and aOR=6.17 (95%CI=1.45; 26.20) (p=0.014); respectively]. When data were stratified by major HCV genotypes, patients infected with HCV genotype 1 (GT1) had significant values for both rs1013151 and rs5744069 polymorphisms [aOR=5.79 (95%CI=1.44; 23.32) (p=0.013) and aOR=8.01 (95%CI=2.16; 35.65) (p=0.005); respectively]. Finally, none of the TLR8 polymorphisms were significantly associated with mild-inflammation or non-steatosis. In conclusion, TLR8 polymorphisms seem to be related to non-progression of liver fibrosis in HIV/HCV coinfected patients, particularly in males and those patients infected with GT1.
Toll样受体8（TLR8）基因多态性与丙型肝炎病毒（HCV）感染有关。本研究旨在评估TLR8基因多态性与HIV/HCV合并感染患者HCV相关结局的关联。我们对220例行肝活检的患者进行了一项横断面研究。采用GoldenGate®分析对TLR8基因多态性进行基因分型。结局变量为无纤维化（F0）、轻度炎症（A0/A1）和无脂肪变性[脂肪性肝细胞（FH）<10%]。采用逻辑回归分析根据TLR8基因多态性比较结局变量。分析了4个多态性位点（rs1013151、rs5744069、rs17256081和rs3764880rs1013151）。女性患者在rs17256081和rs101315位点TLR8主要等位基因频率较高，在rs3764880和rs5744069位点次要等位基因频率较高。男性患者除rs3764880位点主要等位基因频率较高外（p<0.01），TLR8次要等位基因频率较高。两个TLR8基因多态性位点（rs1013151和rs5744069）与无纤维化（F0）显著相关[校正比值比（aOR）分别为4.42（95%置信区间（95%CI）=1.54；12.68）（p=0.006）和aOR=4.76（95%CI=1.69；13.37）（p=0.003）]。按性别分层后，rs1013151和rs5744069多态性对男性患者仍具有显著性[aOR分别为4.49（95%CI=1.08；18.62）（p=0.039）和aOR=6.17（95%CI=1.45；26.20）（p=0.014）]。按主要HCV基因型分层后，感染HCV 1型（GT1）的患者rs1013151和rs5744069多态性位点均具有显著性[aOR分别为5.79（95%CI=1.44；23.32）（p=0.013）和aOR=8.01（95%CI=2.16；35.65）（p=0.005）]。最后，TLR8基因多态性与轻度炎症或无脂肪变性均无显著关联。总之，TLR8基因多态性似乎与HIV/HCV合并感染患者肝纤维化的非进展有关，尤其是男性患者和感染GT1的患者。
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