title: FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.
abstract: BACKGROUND
  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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Alvarez
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarria
authors.forename: Ana
authors.initials: A
authors.lastname: Carrero
authors.forename: Sonia
authors.initials: S
authors.lastname: Vázquez-Morón
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Broncano
authors.forename: Cristina
authors.initials: C
authors.lastname: Diez
authors.forename: Francisco
authors.initials: F
authors.lastname: Tejerina
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000998:Antiviral Agents / Q000627:therapeutic use; D015992:Body Mass Index; D060085:Coinfection / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D011506:Proteins; D012254:Ribavirin; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human