PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients

Abstract

AIM To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients. METHODS Two 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. RESULTS PNPLA3 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. CONCLUSION PNPLA3 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.

DOI: 10.1186/s40064-015-0870-5

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@inproceedings{Nakaoka2015PNPLA3IA, title={PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients}, author={Kazunori Nakaoka and Senju Hashimoto and Naoto Kawabe and Yoshifumi Nitta and Michihito Murao and Takuji Nakano and Hiroaki Shimazaki and Toshiki Kan and Yuka Takagawa and Masashi Ohki and Takamitsu Kurashita and Tomoki Takamura and Toru Nishikawa and Naohiro Ichino and Keisuke Osakabe and Kentaro Yoshioka}, booktitle={SpringerPlus}, year={2015} }