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

Kazunori Nakaoka, Senju Hashimoto, Naoto Kawabe, Yoshifumi Nitta, Michihito Murao, Takuji Nakano, Hiroaki Shimazaki, Toshiki Kan, Yuka Takagawa, Masashi Ohki, Takamitsu Kurashita, Tomoki Takamura, Toru Nishikawa, Naohiro Ichino, Keisuke Osakabe, Kentaro Yoshioka

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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.

Original languageEnglish
JournalSpringerPlus
Volume4
Issue number1
DOIs
Publication statusPublished - 01-01-2015

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Phospholipases
Chronic Hepatitis C
Carcinogenesis
Genotype
Liver
Fibrosis
Interferons
Hepatocellular Carcinoma
Logistic Models
Regression Analysis
Single Nucleotide Polymorphism
Acoustics
Body Mass Index
Therapeutics
Radiation
Recurrence
Health

All Science Journal Classification (ASJC) codes

  • General

Cite this

Nakaoka, K., Hashimoto, S., Kawabe, N., Nitta, Y., Murao, M., Nakano, T., ... Yoshioka, K. (2015). PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients. SpringerPlus, 4(1). https://doi.org/10.1186/s40064-015-0870-5
Nakaoka, Kazunori ; Hashimoto, Senju ; Kawabe, Naoto ; Nitta, Yoshifumi ; Murao, Michihito ; Nakano, Takuji ; Shimazaki, Hiroaki ; Kan, Toshiki ; Takagawa, Yuka ; Ohki, Masashi ; Kurashita, Takamitsu ; Takamura, Tomoki ; Nishikawa, Toru ; Ichino, Naohiro ; Osakabe, Keisuke ; Yoshioka, Kentaro. / PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients. In: SpringerPlus. 2015 ; Vol. 4, No. 1.
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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.",
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",
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Nakaoka, K, Hashimoto, S, Kawabe, N, Nitta, Y, Murao, M, Nakano, T, Shimazaki, H, Kan, T, Takagawa, Y, Ohki, M, Kurashita, T, Takamura, T, Nishikawa, T, Ichino, N, Osakabe, K & Yoshioka, K 2015, 'PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients', SpringerPlus, vol. 4, no. 1. https://doi.org/10.1186/s40064-015-0870-5

PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients. / Nakaoka, Kazunori; Hashimoto, Senju; Kawabe, Naoto; Nitta, Yoshifumi; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Takagawa, Yuka; Ohki, Masashi; Kurashita, Takamitsu; Takamura, Tomoki; Nishikawa, Toru; Ichino, Naohiro; Osakabe, Keisuke; Yoshioka, Kentaro.

In: SpringerPlus, Vol. 4, No. 1, 01.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients

AU - Nakaoka, Kazunori

AU - Hashimoto, Senju

AU - Kawabe, Naoto

AU - Nitta, Yoshifumi

AU - Murao, Michihito

AU - Nakano, Takuji

AU - Shimazaki, Hiroaki

AU - Kan, Toshiki

AU - Takagawa, Yuka

AU - Ohki, Masashi

AU - Kurashita, Takamitsu

AU - Takamura, Tomoki

AU - Nishikawa, Toru

AU - Ichino, Naohiro

AU - Osakabe, Keisuke

AU - Yoshioka, Kentaro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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