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dc.contributor.authorPineda-Tenor, Daniel 
dc.contributor.authorBerenguer, Juan
dc.contributor.authorJimenez-Sousa, Maria Angeles 
dc.contributor.authorGarcia-Alvarez, Monica 
dc.contributor.authorAldámiz-Echevarria, Teresa
dc.contributor.authorCarrero, Ana
dc.contributor.authorVázquez-Morón, Sonia 
dc.contributor.authorTrento, Alfonsina 
dc.contributor.authorDiez, Cristina
dc.contributor.authorTejerina, Francisco
dc.contributor.authorGuzman-Fulgencio, Maria 
dc.contributor.authorResino, Salvador
dc.identifier.citationBMC Med. 2014; 12: 198.
dc.description.abstractBACKGROUND: The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients. METHODS: We carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFNα/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ≥2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR). RESULTS: The rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ≥27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ≥2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%. CONCLUSIONS: Patients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.
dc.description.sponsorshipThis work has been supported by grants given by Fondo de Investigación de Sanidad en España (FIS) [Spanish Health Founds for Research] [grant numbers PI08/0738, PI11/00245; PI08/0928, and PI11/01556], and “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) [grant number 361020/10]. This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT10/009 and INT12/154. PGB, DPT, MGF, MAJS and MGA are supported by “Instituto de Salud Carlos III” [grant numbers FI12/00036, CM12/00043, RD12/0017/0024, CD13/00012and CD12/00442, respectively].
dc.publisherBioMed Central (BMC) 
dc.subjectChronic hepatitis C
dc.subjectHCV therapy
dc.subjectInsulin resistance
dc.titleFTOrs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderFundación para la Investigación y la Prevención del Sida en España 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.identifier.journalBMC Medicine
dc.repisalud.centroISCIII::Centro Nacional de Microbiología::Área de Patología Molecular::Unidad de Infección viral e Inmunidad
dc.rights.accessRightsopen accesses_ES

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