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Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma.
Liu, Y-L; Patman, G L; Leathart, J B S; Piguet, A-C; Burt, A D; Dufour, J-F; Day, C P; Daly, A K; Reeves, H L; Anstee, Q M.
Afiliação
  • Liu YL; Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • Patman GL; Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • Leathart JB; Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • Piguet AC; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland.
  • Burt AD; Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • Dufour JF; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland.
  • Day CP; Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • Daly AK; Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • Reeves HL; Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle upon Tyne, UK. Electronic address: helen.reeves@ncl.ac.uk.
  • Anstee QM; Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
J Hepatol ; 61(1): 75-81, 2014 Jul.
Article em En | MEDLINE | ID: mdl-24607626
ABSTRACT
BACKGROUND &

AIMS:

Subtle inter-patient genetic variation and environmental factors combine to determine disease progression in non-alcoholic fatty liver disease (NAFLD). Carriage of the PNPLA3 rs738409 c.444C >G minor allele (encoding the I148M variant) has been robustly associated with advanced NAFLD. Although most hepatocellular carcinoma (HCC) is related to chronic viral hepatitis or alcoholic liver disease, the incidence of NAFLD-related HCC is increasing. We examined whether rs738409 C >G was associated with HCC-risk in patients with NAFLD.

METHODS:

PNPLA3 rs738409 genotype was determined by allelic discrimination in 100 European Caucasians with NAFLD-related HCC and 275 controls with histologically characterised NAFLD.

RESULTS:

Genotype frequencies were significantly different between NAFLD-HCC cases (CC=28, CG=43, GG=29) and NAFLD-controls (CC=125, CG=117, GG=33) (p=0.0001). In multivariate analysis adjusted for age, gender, diabetes, BMI, and presence of cirrhosis, carriage of each copy of the rs738409 minor (G) allele conferred an additive risk for HCC (adjusted OR 2.26 [95% CI 1.23-4.14], p=0.0082), with GG homozygotes exhibiting a 5-fold [1.47-17.29], p=0.01 increased risk over CC. When compared to the UK general population (1958 British Birth Cohort, n=1476), the risk-effect was more pronounced (GC vs. CC unadjusted OR 2.52 [1.55-4.10], p=0.0002; GG vs. CC OR 12.19 [6.89-21.58], p<0.0001).

CONCLUSIONS:

Carriage of the PNPLA3 rs738409 C >G polymorphism is not only associated with greater risk of progressive steatohepatitis and fibrosis but also of HCC. If validated, these findings suggest that PNPLA3 genotyping has the potential to contribute to multi-factorial patient-risk stratification, identifying those to whom HCC surveillance may be targeted.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Polimorfismo de Nucleotídeo Único / Hepatopatia Gordurosa não Alcoólica / Lipase / Neoplasias Hepáticas / Proteínas de Membrana Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Polimorfismo de Nucleotídeo Único / Hepatopatia Gordurosa não Alcoólica / Lipase / Neoplasias Hepáticas / Proteínas de Membrana Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido
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