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The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients.
Scand J Gastroenterol. 2016 Aug; 51(8):967-73.SJ

Abstract

BACKGROUND AND AIMS

The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C > G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP.

METHODS

Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing.

RESULTS

Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively, p < 0.001), and different between the latter two groups (p < 0.001). Three-quarters (74%) of NASH cirrhotics carried at least one G allele, and almost half of them (46%) were GG homozygous. By multivariate analysis in the NAFLD population, each copy of the G allele was associated with an almost doubling of the risk of cirrhosis [OR 1.8 (1.02-3.2)], while being GG homozygous with a tripled risk compared with being CC homozygous [3.01 (1.03-10.8)].

CONCLUSIONS

In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis.

Authors+Show Affiliations

a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;b Laboratory of Microscopic and Ultrastructural Anatomy, CIR , University Campus Bio-Medico , Rome , Italy ;a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;c Virology Unit , University Campus Bio-Medico , Rome , Italy.a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;b Laboratory of Microscopic and Ultrastructural Anatomy, CIR , University Campus Bio-Medico , Rome , Italy ;c Virology Unit , University Campus Bio-Medico , Rome , Italy.a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27150500

Citation

Vespasiani-Gentilucci, Umberto, et al. "The PNPLA3 Rs738409 C > G Polymorphism Is Associated With the Risk of Progression to Cirrhosis in NAFLD Patients." Scandinavian Journal of Gastroenterology, vol. 51, no. 8, 2016, pp. 967-73.
Vespasiani-Gentilucci U, Gallo P, Porcari A, et al. The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients. Scand J Gastroenterol. 2016;51(8):967-73.
Vespasiani-Gentilucci, U., Gallo, P., Porcari, A., Carotti, S., Galati, G., Piccioni, L., De Vincentis, A., Dell'Unto, C., Vorini, F., Morini, S., Riva, E., & Picardi, A. (2016). The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients. Scandinavian Journal of Gastroenterology, 51(8), 967-73. https://doi.org/10.3109/00365521.2016.1161066
Vespasiani-Gentilucci U, et al. The PNPLA3 Rs738409 C > G Polymorphism Is Associated With the Risk of Progression to Cirrhosis in NAFLD Patients. Scand J Gastroenterol. 2016;51(8):967-73. PubMed PMID: 27150500.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients. AU - Vespasiani-Gentilucci,Umberto, AU - Gallo,Paolo, AU - Porcari,Aldostefano, AU - Carotti,Simone, AU - Galati,Giovanni, AU - Piccioni,Livia, AU - De Vincentis,Antonio, AU - Dell'Unto,Chiara, AU - Vorini,Ferruccio, AU - Morini,Sergio, AU - Riva,Elisabetta, AU - Picardi,Antonio, Y1 - 2016/05/06/ PY - 2016/5/7/entrez PY - 2016/5/7/pubmed PY - 2017/4/25/medline KW - NASH cirrhosis KW - Non-alcoholic fatty liver disease KW - patatin-like phospholipase domain-containing 3 SP - 967 EP - 73 JF - Scandinavian journal of gastroenterology JO - Scand. J. Gastroenterol. VL - 51 IS - 8 N2 - BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C > G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP. METHODS: Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing. RESULTS: Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively, p < 0.001), and different between the latter two groups (p < 0.001). Three-quarters (74%) of NASH cirrhotics carried at least one G allele, and almost half of them (46%) were GG homozygous. By multivariate analysis in the NAFLD population, each copy of the G allele was associated with an almost doubling of the risk of cirrhosis [OR 1.8 (1.02-3.2)], while being GG homozygous with a tripled risk compared with being CC homozygous [3.01 (1.03-10.8)]. CONCLUSIONS: In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis. SN - 1502-7708 UR - https://www.unboundmedicine.com/medline/citation/27150500/The_PNPLA3_rs738409_C_>_G_polymorphism_is_associated_with_the_risk_of_progression_to_cirrhosis_in_NAFLD_patients_ L2 - http://www.tandfonline.com/doi/full/10.3109/00365521.2016.1161066 DB - PRIME DP - Unbound Medicine ER -