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PNPLA 3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C
Author(s) -
Petta S.,
Vanni E.,
Bugianesi E.,
Rosso C.,
Cabibi D.,
Cammà C.,
Di Marco V.,
Eslam M.,
Grimaudo S.,
Macaluso F. S.,
McLeod D.,
Pipitone R. M.,
Abate M. L.,
Smedile A.,
George J.,
Craxì A.
Publication year - 2015
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13169
Subject(s) - steatohepatitis , medicine , steatosis , gastroenterology , fatty liver , fibrosis , genotype , disease , biology , gene , biochemistry
Summary Background The PNPLA 3/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 ). Aim To test in genotype 1(G1)‐ CHC patients, the putative association between the PNPLA 3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Methods Four hundred and thirty‐four consecutively biopsied Caucasian G1‐ CHC patients were genotyped for PNPLA 3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA 3 mRNA was evaluated in 63 patients. Results The prevalence of steatohepatitis increased from 16.5% in patients with PNPLA 3 CC , to 23.2% in CG and 29.2% in the GG genotype ( P = 0.02). By multiple logistic regression, PNPLA 3 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, PNPLA 3 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 PNPLA 3 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). Conclusion In patients with genotype 1 hepatitis C, the PNPLA 3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non‐obese subjects.