title: The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients.
abstract: Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12-3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23-6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01-11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Núñez-Torres
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Mancebo
authors.affiliation: Unit of Infectious Diseases, Reina Sofía University Hospital, Córdoba, Spain.|Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), University of Córdoba, Córdoba, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Frías
authors.affiliation: Department of Medical and Surgical Science for Adults and Children, Clinic and Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dolci
authors.affiliation: Unit of Infectious Diseases, La Línea de la Concepción Hospital, Cádiz, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Téllez
authors.affiliation: Unit of Infectious Diseases, Huelva University Hospital, Huelva, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Merino
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Merchante
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Gómez-Mateos
authors.affiliation: Department of Medical and Surgical Science for Adults and Children, Clinic and Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.affiliation: Unit of Infectious Diseases, Reina Sofía University Hospital, Córdoba, Spain.|Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), University of Córdoba, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juárez
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.|Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Real
mesh_terms: D000328:Adult; D000483:Alleles; D060085:Coinfection / Q000821:virology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D054459:Elasticity Imaging Techniques; D005234:Fatty Liver / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D005819:Genetic Markers; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent