Genetic polymorphisms of apolipoproteins A-IV, E and H in Koreans
HUMAN HEREDITY
Authors: Kim, HS; Kamboh, MI
Abstract
A South Korean population from Kongju (n = 350) was screened by isoelectric focusing and immunoblotting procedures to determine the distribution of genetic variations in 3 apolipoprotein genes including APOA-TV, APOE and APOH. Although the known APOA-IV protein polymorphism was not observed, sporadic examples of 2 putative new variants were identified. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.069, 0.823 and 0.107, respectively. At the APOH structural locus 3 common alleles, APOH*1 (0.010), APOH*2 (0.913) and APOH*3 (0.073) were observed. In addition, a unique APOH allele designated APOH*3 Kongju was identified in this Korean population.
Plasma apolipoprotein H limits HCV replication and associates with response to NS3 protease inhibitors-based therapy
LIVER INTERNATIONAL
Authors: Sultanik, Philippe; Mallet, Vincent; Lagaye, Sylvie; Casrouge, Armanda; Dorival, Celine; Barthe, Yoann; Fontaine, Helene; Hezode, Christophe; Mottez, Estelle; Bronowicki, Jean-Pierre; Carrat, Fabrice; Theodorou, Ioannis; Abel, Laurent; Gayat, Etienne; Fontanet, Arnaud; Pol, Stanislas; Albert, Matthew L.
Abstract
Background & AimsChronic infection with HCV remains a public health problem with approximately 150 million people infected worldwide. HCV intersects with lipid metabolism for replication and entry; and plasma concentrations of apolipoproteins have been identified as predictors for response to therapy. Herein, we conducted a screen of plasma proteins, including all apolipoproteins, to identify correlates of response to pegylated-interferon/ribavirin (PR) and HCV non-structural protein 3 (NS3) inhibitors (i.e., telaprevir/boceprevir) therapy in treatment-experienced cirrhotic patients from the ANRS CUPIC cohort. MethodsWe analysed 220 baseline plasma protein concentrations in 189 patients using Luminex technology and analyzed results. ResultsWe identified baseline levels of apolipoprotein H (apoH) as a surrogate marker for sustained virological response (SVR). Notably, increased plasma concentration of apoH, used in combination with known clinical parameters, established a robust model with improved classification of patients as likely to achieve SVR (AUC=0.77, Se=66%, Sp=72%, NRI=39%). Moreover, we provide mechanistic information that indicates a previously unidentified role for apoH during viral entry. Using a human liver slices HCV infection model, we demonstrate that apoH limits replication. ConclusionThese data support testing of new biomarker strategies for the management of cirrhotic HCV patients and expand our understanding of how apoH may intersect with HCV infection.