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

Journal article
Authors Karolina Rembeck
Cristina Maglio
Martin Lagging
Peer Brehm Christensen
Martti Färkkilä
Nina Langeland
Mads Rauning Buhl
Court Pedersen
Kristine Mørch
Gunnar Norkrans
Kristoffer Hellstrand
Magnus Lindh
Carlo Pirazzi
Maria Antonella Burza
Stefano Romeo
Johan Westin
Published in BMC medical genetics
Volume 13
Issue 1
Pages 82
ISSN 1471-2350
Publication year 2012
Published at Institute of Biomedicine, Department of Infectious Medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 82
Language en
Keywords Hepatitis C, PNPLA 3, Insulin resistance, Viral load
Subject categories Basic Medicine


ABSTRACT: BACKGROUND: Hepatic 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. METHODS: Three hundred and eighty-two treatment naive 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. RESULTS: In HCV genotype 2 infected patients carrying the PNPLA3 148 M 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. CONCLUSIONS: Our results suggest a possible association between the PNPLA3 148 M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

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