Viral genotype-specific role of PNPLA3 , PPARG , MTTP, and IL28B in hepatitis C virus-associated steatosis

Cai, Tao; Dufour, Jean–François; Muellhaupt, Beat; Gerlach, Tilman; Heim, Markus H.; Moradpour, Darius; Cerny, Andreas; Malinverni, Raffaele; Kaddai, Vincent; Bochud, Murielle; Negro, Francesco; Bochud, Pierre‐Yves

doi:10.1016/j.jhep.2010.12.020

Cited by 103 publications

(97 citation statements)

References 39 publications

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“…A significant interaction between age at infection and rs738409 [G] has also been reported in one study [37]. In addition, the association with steatosis was found to be less pronounced [38], or even absent, in patients with HCV genotype-3 infection [33,34]. It is likely that the stronger effect of ''environmental injurious exposure" (here HCV) downplayed the impact of PNPLA3 on steatosis and fibrosis in CHC.…”

Section: Key Pointmentioning

confidence: 66%

See 1 more Smart Citation

PNPLA3 gene in liver diseases

Trépo

Romeo

Zucman‐Rossi

et al. 2016

Journal of Hepatology

231

196

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Section: Key Pointmentioning

confidence: 66%

“…In CHC, a significant association of rs738409 [G] with steatosis [32][33][34][35], and/or fibrosis [32,34,35] was observed in several independent European cohorts following adjustment for other known environmental risk factors. The association with fibrosis has now been confirmed…”

Section: Chronic Viral Hepatitis B and Cmentioning

confidence: 99%

PNPLA3 gene in liver diseases

Trépo

Romeo

Zucman‐Rossi

et al. 2016

Journal of Hepatology

231

196

View full text Add to dashboard Cite

“…Valenti et al also reported that the rs738409 genotype, a polymorphism that influences liver fat without affecting insulin resistance and body composition, was associated with severe hepatic steatosis in patients infected with a non-3 HCV genotype, and also with fibrosis stage and cirrhosis (OR = 1.47; p = 0.002). [36] Similarly, Cai et al [37] reported that rs738409 was associated with an increased risk of steatosis in patients infected with a non-3 HCV genotype. These results suggest distinct pathogenic mechanisms in the 3 and non-3 genotypes.…”

Section: Editorialmentioning

confidence: 97%

HCV genotype 3: a wolf in sheep’s clothing

Blanco

Rivero‐Juárez

2016

Expert Review of Anti-infective Therapy

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“…[5][6][7] Some studies on cohorts of mostly genotype 1 (G1) chronic hepatitis C (CHC) patients have reported an association between the PNPLA3 rs738409 G variant and the severity of both steatosis and fibrosis, the risk of fibrosis progression and HCC occurrence, and the response to pegylated interferon plus ribavirin therapy. [8][9][10][11][12][13][14][15] Bedossa et al, in liver biopsies from CHC patients, recently characterised the presence of histological features of steatohepatitis, showing that the occurrence of NASH in this setting not only was related to a poor atrisk metabolic profile but was also a risk factor for the severity of liver damage. 16 This study however did not investigate the impact of genetic background on the presence of steatohepatitis in the context of CHC.…”

Section: Introductionmentioning

confidence: 99%

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C

Petta

Vanni²,

Bugianesi³

et al. 2015

Aliment Pharmacol Ther

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SummaryBackgroundThe PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non‐alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC).AimTo test in genotype 1(G1)‐CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis.MethodsFour hundred and thirty‐four consecutively biopsied Caucasian G1‐CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients.ResultsThe prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype (P = 0.02). By multiple logistic regression, PNPLA3 genotype (OR 1.54, 95% CI 1.03–2.30, P = 0.03), together with age (OR 1.03, 95% CI 1.00–1.05, P = 0.02), BMI ≥ 30 (OR 2.06, 95% CI 1.04–4.10, P = 0.03) and homoeostasis model assessment (HOMA, OR 1.18, 95% CI 1.04–1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non‐obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders (OR 2.06, 95% CI 1.26–3.36, P = 0.004). We showed an independent association between steatohepatitis (OR 2.05, 95% CI 1.05–4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA (P = 0.002).ConclusionIn patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non‐obese subjects.

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Viral genotype-specific role of PNPLA3 , PPARG , MTTP, and IL28B in hepatitis C virus-associated steatosis

Cited by 103 publications

References 39 publications

PNPLA3 gene in liver diseases

PNPLA3 gene in liver diseases

HCV genotype 3: a wolf in sheep’s clothing

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C

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