Journal article
Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma.
- 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.
- 2014-03-11
Published in:
- Journal of hepatology. - 2014
Gene
HCC
Hepatocellular carcinoma
NAFLD
NASH
PNPLA3
Steatohepatitis
Adult
Aged
Carcinoma, Hepatocellular
Case-Control Studies
Cohort Studies
Disease Progression
European Continental Ancestry Group
Female
Gene Frequency
Genetic Association Studies
Homozygote
Humans
Lipase
Liver Neoplasms
Male
Membrane Proteins
Middle Aged
Non-alcoholic Fatty Liver Disease
Polymorphism, Single Nucleotide
Risk Factors
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.jhep.2014.02.030
- PMID 24607626
- Persistent URL
- https://sonar.ch/global/documents/144192
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