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Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunodeficiency virus-infected patients

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World Journal of virology 2017年第2期6卷 36-45页

作者： julio collazos.eulalia v.lle-garay Tomás Suárez-Zarracina Angel-Hugo Montes José A Cartón víctor Asensi Infectious Diseases Hospital de Galdácano Biochemistry and Molecular Biology Hospital Universitario Central de AsturiasOviedo University School of Medicine Infectious Diseases Hospital Universitario Central de AsturiasOviedo University School of Medicine

AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIv)-infected *** Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIv-infected individuals with/out hepatitis C virus(HCv) coinfection. A total of 158 patients were included, 57 of whom were HCvcoinfected. All patients drank verse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP *** A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCv-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ *** Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis

关键词： Human immunodeficiency virus Hepatitis C virus Liver fibrosis Transient elastometry Noninvasive fibrosis markers Metalloproteases Their tissue inhibitors Genetic polymorphisms

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Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

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World Journal of virology 2015年第3期4卷 169-177页

作者： victor Asensi julio collazos.eulalia v.lle-garay Infectious Diseases-HIv Unit Hospital Universitario Central de AsturiasOviedo University School of Medicine Infectious Diseases Unit Hospital de Galdácano Biochemistry and Molecular Biology Department Oviedo University School of Medicine

Pharmacogenetics refers to the effect of single nucleotide polymorphisms(SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction(HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus(HIv) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIv-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1(MDR1) 3435 C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity.

关键词： Pharmacogenomics Pharmacokinetics Antiretroviral drugs Adverse effects Human immunodeficiency virus infection Single nucleotide polymorphisms

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