PNPLA 3I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

BMC Medical Genetics

Research Article

Martti Färkkilä¹  Mads Rauning Buhl²  Peer Brehm Christensen³  Court Pedersen³  Gunnar Norkrans⁴  Magnus Lindh⁴  Kristoffer Hellstrand⁴  Johan Westin⁴  Martin Lagging⁴  Karolina Rembeck⁴  Nina Langeland⁵  Kristine Mørch⁵  Maria Antonella Burza⁶  Cristina Maglio⁶  Stefano Romeo⁶  Carlo Pirazzi⁶ 

[1] Department of Gastroenterology, Helsinki University, Helsinki, Finland;Department of Infectious Diseases, Aarhus University, Aarhus, Denmark;Department of Infectious Diseases, University of Southern Denmark, Odense, Denmark;Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;Department of Medicine, Haukeland University Hospital and Institute of Medicine, University of Bergen, Bergen, Norway;Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;

关键词: Hepatitis C;    PNPLA 3;    Insulin resistance;    Viral load;   

DOI  :  10.1186/1471-2350-13-82

 received in 2012-03-27, accepted in 2012-06-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients.MethodsThree hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients.ResultsIn HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients.ConclusionsOur results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

【 授权许可】

Unknown   
© Rembeck et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.