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

BMC Medical Genetics

Johan Westin⁴  Stefano Romeo³  Maria Antonella Burza³  Carlo Pirazzi³  Magnus Lindh⁴  Kristoffer Hellstrand⁴  Gunnar Norkrans⁴  Kristine Mørch⁶  Court Pedersen²  Mads Rauning Buhl¹  Nina Langeland⁶  Martti Färkkilä⁵  Peer Brehm Christensen²  Martin Lagging⁴  Cristina Maglio³  Karolina Rembeck⁴ 

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

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

Others  :  1177800
DOI  :  10.1186/1471-2350-13-82

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

【 摘 要 】

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 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.

Results

In 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.

Conclusions

Our 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】

   
2012 Rembeck et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

Figure 2 .

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