PNPLA3 rs738409 G allele carriers with genotype 1b HCV cirrhosis have lower viral load but develop liver failure at younger age.
Alleles
Carcinoma, Hepatocellular
/ genetics
Case-Control Studies
Cross-Sectional Studies
Female
Genetic Predisposition to Disease
/ genetics
Genotype
Hepatitis C, Chronic
/ genetics
Humans
Lipase
/ genetics
Liver
/ virology
Liver Cirrhosis
/ genetics
Liver Failure
/ genetics
Liver Neoplasms
/ genetics
Liver Transplantation
/ methods
Male
Membrane Proteins
/ genetics
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
Retrospective Studies
Viral Load
/ methods
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
19
05
2019
accepted:
03
09
2019
entrez:
19
9
2019
pubmed:
19
9
2019
medline:
7
3
2020
Statut:
epublish
Résumé
PNPLA3 rs738409 minor allele c.444G represents a risk factor for liver steatosis and fibrosis progression also in chronic hepatitis C (HCV). We investigated its impact on the timing of liver transplantation (LT) in patients with genotype 1b HCV cirrhosis. We genotyped and evaluated 172 LT candidates with liver cirrhosis owing to chronic HCV infection, genotype 1b. One hundred patients needed LT for chronic liver failure (CLF) and 72 for a small hepatocellular carcinoma (HCC) in the cirrhotic liver without CLF. Population controls (n = 647) were selected from the Czech cross-sectional study MONICA. The CLF patients were younger (53.5 ± 7.2 vs. 59.6 ± 6.6, P < 0.001) with more advanced liver disease than HCC patients (Child-Pugh's score 9.1 ± 1.8 vs. 7.1 ± 1.9, P < 0.001, MELD 14.1 ± 3.9 vs. 11.1 ± 3.7, P < 0.001). PNPLA3 G allele increased the risk of LT for CLF in both allelic and recessive models (CG + GG vs. CC: OR, 1.90; 95% CI, 1.017-3.472, P = 0.045 and GG vs. CC + CG: OR, 2.94; 95% CI, 1.032-7.513, P = 0.042). Multivariate analysis identified younger age (P < 0.001) and the G allele (P < 0.05) as risk factors for CLF. The genotype frequencies between the CLF group and MONICA study significantly differed in both, allelic and recessive model (P = 0.004, OR 1.87, 95% CI 1.222-2.875; P < 0.001, OR 3.33, 95% CI 1.824-6.084, respectively). The OR values almost doubled in the recessive model compared with the allelic model suggesting the additive effect of allele G. In contrast, genotype frequencies in the HCC group were similar to the MONICA study in both models. Pretransplant viral load was significantly lower in GG than in CC + CG genotypes (median, IQR; 162,500 (61,550-319,000) IU/ml vs. 570,000 (172,000-1,595,000) IU/ml, P < 0.0009). Our results suggest that PNPLA3 rs738409 G allele carriage may be associated with a faster progression of HCV cirrhosis to chronic liver failure.
Sections du résumé
BACKGROUND
PNPLA3 rs738409 minor allele c.444G represents a risk factor for liver steatosis and fibrosis progression also in chronic hepatitis C (HCV). We investigated its impact on the timing of liver transplantation (LT) in patients with genotype 1b HCV cirrhosis.
METHODS
We genotyped and evaluated 172 LT candidates with liver cirrhosis owing to chronic HCV infection, genotype 1b. One hundred patients needed LT for chronic liver failure (CLF) and 72 for a small hepatocellular carcinoma (HCC) in the cirrhotic liver without CLF. Population controls (n = 647) were selected from the Czech cross-sectional study MONICA.
RESULTS
The CLF patients were younger (53.5 ± 7.2 vs. 59.6 ± 6.6, P < 0.001) with more advanced liver disease than HCC patients (Child-Pugh's score 9.1 ± 1.8 vs. 7.1 ± 1.9, P < 0.001, MELD 14.1 ± 3.9 vs. 11.1 ± 3.7, P < 0.001). PNPLA3 G allele increased the risk of LT for CLF in both allelic and recessive models (CG + GG vs. CC: OR, 1.90; 95% CI, 1.017-3.472, P = 0.045 and GG vs. CC + CG: OR, 2.94; 95% CI, 1.032-7.513, P = 0.042). Multivariate analysis identified younger age (P < 0.001) and the G allele (P < 0.05) as risk factors for CLF. The genotype frequencies between the CLF group and MONICA study significantly differed in both, allelic and recessive model (P = 0.004, OR 1.87, 95% CI 1.222-2.875; P < 0.001, OR 3.33, 95% CI 1.824-6.084, respectively). The OR values almost doubled in the recessive model compared with the allelic model suggesting the additive effect of allele G. In contrast, genotype frequencies in the HCC group were similar to the MONICA study in both models. Pretransplant viral load was significantly lower in GG than in CC + CG genotypes (median, IQR; 162,500 (61,550-319,000) IU/ml vs. 570,000 (172,000-1,595,000) IU/ml, P < 0.0009).
CONCLUSIONS
Our results suggest that PNPLA3 rs738409 G allele carriage may be associated with a faster progression of HCV cirrhosis to chronic liver failure.
Identifiants
pubmed: 31527889
doi: 10.1371/journal.pone.0222609
pii: PONE-D-19-14130
pmc: PMC6748417
doi:
Substances chimiques
Membrane Proteins
0
Lipase
EC 3.1.1.3
adiponutrin, human
EC 3.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0222609Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Hepatology. 2001 Jun;33(6):1394-403
pubmed: 11391528
Virology. 2004 Jul 1;324(2):450-61
pubmed: 15207630
Nat Genet. 2008 Dec;40(12):1461-5
pubmed: 18820647
N Engl J Med. 2008 Dec 4;359(23):2429-41
pubmed: 19052125
Lancet Oncol. 2009 Jan;10(1):35-43
pubmed: 19058754
Hepatology. 2010 Apr;51(4):1209-17
pubmed: 20373368
Atherosclerosis. 2010 Aug;211(2):676-81
pubmed: 20471016
Hepatology. 2010 Sep;52(3):904-12
pubmed: 20648472
J Biol Chem. 2011 Jan 28;286(4):3018-32
pubmed: 21056986
Nat Protoc. 2011 Feb;6(2):121-33
pubmed: 21293453
Liver Int. 2011 Sep;31(8):1137-43
pubmed: 21745286
J Viral Hepat. 2011 Oct;18(10):e516-22
pubmed: 21914071
Hepatology. 2012 Apr;55(4):1307-8
pubmed: 22162034
BMC Med Genet. 2012 Sep 14;13:82
pubmed: 22978414
Clin Infect Dis. 2013 Jul;57(2):230-6
pubmed: 23616492
Hepatology. 2014 Jun;59(6):2170-7
pubmed: 24114809
Am J Gastroenterol. 2014 Mar;109(3):325-34
pubmed: 24445574
Nat Genet. 2014 Apr;46(4):352-6
pubmed: 24531328
J Hepatol. 2014 Jul;61(1):75-81
pubmed: 24607626
J Lipid Res. 2015 Jan;56(1):167-75
pubmed: 25378656
J Hepatol. 2015 Mar;62(3):512-8
pubmed: 25457210
Sci Rep. 2015 Mar 20;5:9284
pubmed: 25791171
Am J Gastroenterol. 2015 Jun;110(6):846-56
pubmed: 25964223
Hepatobiliary Surg Nutr. 2015 Jun;4(3):152-60
pubmed: 26151055
Clin Gastroenterol Hepatol. 2016 Feb;14(2):295-300
pubmed: 26305067
Gut Liver. 2016 May 23;10(3):456-63
pubmed: 26419236
J Hepatol. 2016 Feb;64(2):433-485
pubmed: 26597456
PLoS One. 2015 Nov 23;10(11):e0143429
pubmed: 26599080
Clin Microbiol Infect. 2016 Apr;22(4):372-378
pubmed: 26806136
Hepatology. 2016 Jul;64(1):34-46
pubmed: 26822232
Scand J Gastroenterol. 2016 Aug;51(8):967-73
pubmed: 27150500
J Hepatol. 2017 Mar;66(3):485-493
pubmed: 27780714
PLoS One. 2016 Dec 14;11(12):e0168265
pubmed: 27973562
J Hepatol. 2017 Dec;67(6):1168-1176
pubmed: 28842296
BMC Infect Dis. 2017 Dec 19;17(1):780
pubmed: 29258449
Dig Liver Dis. 2018 May;50(5):490-495
pubmed: 29396131
N Engl J Med. 2018 Mar 22;378(12):1096-1106
pubmed: 29562163
J Clin Virol. 2018 Jun;103:71-74
pubmed: 29674183
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Sep;1863(9):1041-1056
pubmed: 29885363
J Hepatol. 2018 Oct;69(4):810-817
pubmed: 29940268
Dig Dis Sci. 2018 Nov;63(11):2969-2974
pubmed: 30218427
Int J Cancer. 2019 Feb 1;144(3):533-544
pubmed: 30289982
World J Gastroenterol. 2018 Oct 14;24(38):4403-4411
pubmed: 30344424
Hepatology. 2019 Jun;69(6):2427-2441
pubmed: 30802989
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9521-9526
pubmed: 31019090
N Engl J Med. 1996 Mar 14;334(11):693-9
pubmed: 8594428