title: PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV-coinfected patients under HCV therapy.
abstract: OBJECTIVE
  To analyze whether peroxisome proliferator-activated receptor gamma (PPARγ2) rs1801282 (Pro12Ala) polymorphism is associated with the response to pegylated-interferon-alpha plus ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients, and whether it is able to predict the outcome of HCV treatment.
  
  
  METHODS
  Retrospective follow-up study.
  
  
  METHODS
  Two hundred eighty-five naive patients, who started HCV-treatment, were genotyped for PPARγ2 and interleukin 28B polymorphisms. Genetic data were analyzed under dominant inheritance model. Sustained virological response (SVR) was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment.
  
  
  RESULTS
  The variables significantly associated with SVR in a multivariate analysis were HCV-genotype (GT) 3 {adjusted odds ratio [aOR] = 7.66 [95% of confidence interval (95% CI): 3.96 to 14.81] P < 0.001}, HCV-viremia <500,000 IU/mL [aOR = 2.20 (95% CI: 1.16 to 4.15] P = 0.015), no/mild liver fibrosis (F < 2) [aOR = 1.92 (95% CI: 1.08 to 3.42) P = 0.026], IL28B rs12980275 AA genotype [aOR = 2.70 (95% CI: 1.54 to 4.71) P < 0.001], and PPARγ2 rs1801282 CG/GG genotype [aOR = 2.93 (95% CI: 1.27 to 6.72) P = 0.011]. When PPARγ2 rs1801282 genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly classified was 71.6% and the area under the receiver operating characteristic curves was 0.766 ± 0.028.
  
  
  CONCLUSIONS
  The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with increased odds for achieving SVR in HIV/HCV-coinfected patients on HCV treatment.
authors: *Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; †Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón," Madrid, Spain; ‡Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; §IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid Spain; and ‖Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain.
authors: Amanda
authors: A
authors: Fernández-Rodríguez
authors: Juan
authors: J
authors: Berenguer
authors: Norma
authors: N
authors: Rallón
authors: María A
authors: MA
authors: Jiménez-Sousa
authors: Juan Carlos
authors: JC
authors: López
authors: Vicente
authors: V
authors: Soriano
authors: Mónica
authors: M
authors: García-Álvarez
authors: Jaime
authors: J
authors: Cosín
authors: Paula
authors: P
authors: Martínez
authors: María
authors: M
authors: Guzmán-Fulgencio
authors: Pilar
authors: P
authors: Miralles
authors: José
authors: J
authors: Miguel Benito
authors: Salvador
authors: S
authors: Resino
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D013995:Time; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D047495:PPAR gamma; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda