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Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data.
Hepatology. 2014 Jun; 59(6):2170-7.Hep

Abstract

The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 × 10(-7)). This association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 × 10(-15)) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 × 10(-2)). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC.

CONCLUSION

Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development.

Authors+Show Affiliations

Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24114809

Citation

Trépo, Eric, et al. "Association Between the PNPLA3 (rs738409 C>G) Variant and Hepatocellular Carcinoma: Evidence From a Meta-analysis of Individual Participant Data." Hepatology (Baltimore, Md.), vol. 59, no. 6, 2014, pp. 2170-7.
Trépo E, Nahon P, Bontempi G, et al. Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data. Hepatology. 2014;59(6):2170-7.
Trépo, E., Nahon, P., Bontempi, G., Valenti, L., Falleti, E., Nischalke, H. D., Hamza, S., Corradini, S. G., Burza, M. A., Guyot, E., Donati, B., Spengler, U., Hillon, P., Toniutto, P., Henrion, J., Franchimont, D., Devière, J., Mathurin, P., Moreno, C., ... Deltenre, P. (2014). Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data. Hepatology (Baltimore, Md.), 59(6), 2170-7. https://doi.org/10.1002/hep.26767
Trépo E, et al. Association Between the PNPLA3 (rs738409 C>G) Variant and Hepatocellular Carcinoma: Evidence From a Meta-analysis of Individual Participant Data. Hepatology. 2014;59(6):2170-7. PubMed PMID: 24114809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data. AU - Trépo,Eric, AU - Nahon,Pierre, AU - Bontempi,Gianluca, AU - Valenti,Luca, AU - Falleti,Edmondo, AU - Nischalke,Hans-Dieter, AU - Hamza,Samia, AU - Corradini,Stefano Ginanni, AU - Burza,Maria Antonella, AU - Guyot,Erwan, AU - Donati,Benedetta, AU - Spengler,Ulrich, AU - Hillon,Patrick, AU - Toniutto,Pierluigi, AU - Henrion,Jean, AU - Franchimont,Denis, AU - Devière,Jacques, AU - Mathurin,Philippe, AU - Moreno,Christophe, AU - Romeo,Stefano, AU - Deltenre,Pierre, Y1 - 2014/04/25/ PY - 2013/05/16/received PY - 2013/09/19/accepted PY - 2013/10/12/entrez PY - 2013/10/12/pubmed PY - 2014/8/13/medline SP - 2170 EP - 7 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 59 IS - 6 N2 - UNLABELLED: The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 × 10(-7)). This association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 × 10(-15)) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 × 10(-2)). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC. CONCLUSION: Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/24114809/Association_between_the_PNPLA3__rs738409_C>G__variant_and_hepatocellular_carcinoma:_Evidence_from_a_meta_analysis_of_individual_participant_data_ L2 - https://doi.org/10.1002/hep.26767 DB - PRIME DP - Unbound Medicine ER -