Abstract
AimTo investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients.MethodsTwo hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment.ResultsPNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03–1.09; p < 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03–1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97–4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02–1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13–9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07–1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15–5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90–3.71); p = 0.0936) as the factors independently associated with HCC.ConclusionPNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.
Highlights
It is estimated that 130–170 million people, approximately 2%–3% of the world’s population, are infected with the hepatitis C virus (HCV) (Shepard et al 2005)
The rs738409 single nucleotide polymorphism (SNP) encoding for a functional I148M protein variant of the patatin-like phospholipase domain-containing 3 (PNPLA3, adiponutrin) gene is associated with hepatic steatosis, inflammation, fibrosis, and carcinogenesis in nonalcoholic fatty liver disease (NAFLD) (Romeo et al 2008; Rotman et al 2010; Kawaguchi et al 2012; Kitamoto et al 2013)
In this study, we demonstrated that a PNPLA3 gene polymorphism was associated with the progression of fibrosis to cirrhosis and development of hepatocellular carcinoma (HCC), the association with cirrhosis was only a tendency by multivariable analysis in all the 231 patients studied
Summary
It is estimated that 130–170 million people, approximately 2%–3% of the world’s population, are infected with the hepatitis C virus (HCV) (Shepard et al 2005). The rs738409 single nucleotide polymorphism (SNP) encoding for a functional I148M protein variant of the patatin-like phospholipase domain-containing 3 (PNPLA3, adiponutrin) gene is associated with hepatic steatosis, inflammation, fibrosis, and carcinogenesis in nonalcoholic fatty liver disease (NAFLD) (Romeo et al 2008; Rotman et al 2010; Kawaguchi et al 2012; Kitamoto et al 2013). The association of this PNPLA3 gene polymorphism and pathological features remains to be validated
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