TY - JOUR

T1 - Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis

AU - Paquette, Martine

AU - Gauthier, Dany

AU - Chamberland, Ann

AU - Prat, Annik

AU - De Lucia Rolfe, Emanuella

AU - Rasmussen, Jon J

AU - Kaduka, Lydia

AU - Seidah, Nabil G

AU - Bernard, Sophie

AU - Christensen, Dirk L

AU - Baass, Alexis

N1 - Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

PY - 2020

Y1 - 2020

N2 - BACKGROUND: In parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial.OBJECTIVE: The objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals.METHODS: Total PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans.RESULTS: In a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (β = 0.102, P = 0.008), alkaline phosphatase (β = 0.201, P < 0.0001), ALT (β = 0.238, P < 0.0001), AST (β = 0.120, P = 0.003) and GGT (β = 0.103, P = 0.007) and negatively associated with total bilirubin (β = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05-2.08, P = 0.02).CONCLUSION: Our data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.

AB - BACKGROUND: In parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial.OBJECTIVE: The objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals.METHODS: Total PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans.RESULTS: In a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (β = 0.102, P = 0.008), alkaline phosphatase (β = 0.201, P < 0.0001), ALT (β = 0.238, P < 0.0001), AST (β = 0.120, P = 0.003) and GGT (β = 0.103, P = 0.007) and negatively associated with total bilirubin (β = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05-2.08, P = 0.02).CONCLUSION: Our data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.

U2 - 10.1016/j.clinbiochem.2020.01.003

DO - 10.1016/j.clinbiochem.2020.01.003

M3 - Journal article

C2 - 31972148

VL - 77

SP - 20

EP - 25

JO - Clinical Biochemistry

JF - Clinical Biochemistry

SN - 0009-9120

ER -