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PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C.
Ann Hepatol. 2014 Jul-Aug; 13(4):356-63.AH

Abstract

BACKGROUND

Hepatitis C virus (HCV) is associated with a higher prevalence of steatosis compared to the general population.

AIM

Our aim was to assess the impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients.

MATERIAL AND METHODS

We included 474 HCV patients treated with peginterferon plus ribavirin. PNPLA3 rs738409 was genotyped and patients were classified according to alleles and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using Real Time-PCR.

RESULTS

PNPLA3 allele-G was associated with steatosis [54.1% (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3 [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p = 0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442). Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84 (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017], HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72 (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 ± 0.2), while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5 ± 0.2).

CONCLUSION

PNPLA3 allele-G modulated the development of steatosis, particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3 regulated. Gene interaction may result in differential PNPLA3 gene expression levels in HCV infection.

Authors+Show Affiliations

Unit for Clinical Management of Digestive Diseases and ciberehd, Valme University Hospital, Sevilla, Spain.Unit for Clinical Management of Digestive Diseases and ciberehd, Valme University Hospital, Sevilla, Spain.Unit for Clinical Management of Digestive Diseases and ciberehd, Valme University Hospital, Sevilla, Spain.Immunology Unit, Virgen del Rocio Hospital, Sevilla, Spain. ‡ Mar Hospital, Barcelona, Spain.Mar Hospital, Barcelona, Spain.Digestive Unit and ciberehd. Virgen de la Victoria University Hospital, Málaga, Spain.Virgen de la Arraixaca University Hospital, Murcia, Spain.Costa del Sol Hospital, Marbella, Spain.Puerta de Hierro Hospital, Madrid, Spain.Hepatology Unit and ciberehd. Vall d'Hebrón Hospital, Barcelona, Spain.Immunology Unit, Virgen del Rocio Hospital, Sevilla, Spain.Hepatology Unit and ciberehd. Vall d'Hebrón Hospital, Barcelona, Spain.Digestive Department, Valencia Hospital, Spain.Digestive Unit and ciberehd. Carlos III Hospital, Madrid, Spain.Unit for Clinical Management of Digestive Diseases and ciberehd, Valme University Hospital, Sevilla, Spain.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24927606

Citation

Ampuero, Javier, et al. "PNPLA3 Rs738409 Causes Steatosis According to Viral & IL28B Genotypes in Hepatitis C." Annals of Hepatology, vol. 13, no. 4, 2014, pp. 356-63.
Ampuero J, Del Campo JA, Rojas L, et al. PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C. Ann Hepatol. 2014;13(4):356-63.
Ampuero, J., Del Campo, J. A., Rojas, L., García-Lozano, J. R., Solá, R., Andrade, R., Pons, J. A., Navarro, J. M., Calleja, J. L., Buti, M., González-Escribano, M. F., Forns, X., Diago, M., García-Samaniego, J., & Romero-Gómez, M. (2014). PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C. Annals of Hepatology, 13(4), 356-63.
Ampuero J, et al. PNPLA3 Rs738409 Causes Steatosis According to Viral & IL28B Genotypes in Hepatitis C. Ann Hepatol. 2014 Jul-Aug;13(4):356-63. PubMed PMID: 24927606.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C. AU - Ampuero,Javier, AU - Del Campo,José A, AU - Rojas,Lourdes, AU - García-Lozano,José R, AU - Solá,Ricard, AU - Andrade,Raúl, AU - Pons,José A, AU - Navarro,José M, AU - Calleja,José L, AU - Buti,María, AU - González-Escribano,María F, AU - Forns,Xavier, AU - Diago,Moisés, AU - García-Samaniego,Javier, AU - Romero-Gómez,Manuel, PY - 2014/6/14/entrez PY - 2014/6/14/pubmed PY - 2015/2/3/medline SP - 356 EP - 63 JF - Annals of hepatology JO - Ann Hepatol VL - 13 IS - 4 N2 - BACKGROUND: Hepatitis C virus (HCV) is associated with a higher prevalence of steatosis compared to the general population. AIM: Our aim was to assess the impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients. MATERIAL AND METHODS: We included 474 HCV patients treated with peginterferon plus ribavirin. PNPLA3 rs738409 was genotyped and patients were classified according to alleles and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using Real Time-PCR. RESULTS: PNPLA3 allele-G was associated with steatosis [54.1% (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3 [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p = 0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442). Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84 (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017], HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72 (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 ± 0.2), while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5 ± 0.2). CONCLUSION: PNPLA3 allele-G modulated the development of steatosis, particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3 regulated. Gene interaction may result in differential PNPLA3 gene expression levels in HCV infection. SN - 1665-2681 UR - https://www.unboundmedicine.com/medline/citation/24927606/PNPLA3_rs738409_causes_steatosis_according_to_viral_&_IL28B_genotypes_in_hepatitis_C_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1665-2681(19)30842-7 DB - PRIME DP - Unbound Medicine ER -