PPAR2 Pro12Ala Polymorphism Is Associated With Sustained Virological Response in HIV/HCV-Coinfected Patients Under HCV Therapy

Fernández-Rodríguez, Amanda PhD*; Berenguer, Juan MD, PhD†,‡; Rallón, Norma PhD§; Jiménez-Sousa, María A. PhD*; López, Juan Carlos MD, PhD; Soriano, Vicente MD, PhD; García-Álvarez, Mónica PhD*; Cosín, Jaime MD, PhD; Martínez, Paula PhD§; Guzmán-Fulgencio, María PhD*; Miralles, Pilar MD; Miguel Benito, José MD, PhD§; Resino, Salvador PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 October 2014 - Volume 67 - Issue 2 - p 113–119
doi: 10.1097/QAI.0000000000000282
Basic and Translational Science

Objectives: 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.

Design: 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.

*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.

Correspondence to: Salvador Resino, PhD, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2; 28220 Majadahonda, Madrid, Spain (e-mail: sresino@isciii.es).

Supported by grants given by Fondo de Investigacion de Sanidad en España (FIS) (Spanish Health Founds for Research) (Grant Nos. PI08/0738, PI11/00245; PI11/00870, PI08/0928, and PI11/01556), Red Española de Investigación en SIDA (RIS) (AIDS Research Network) (Grant Nos. RD12/0017/0024, RD12/0017/0004, and RD12/0017/0031), “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) (Grant No. 361020/10). This work has been funded by the Grants RD12/0017/0024 and RD12/0017/0004 as part of the National R + D + I and cofinanced by the ISCIII-General Subdirectorate for Assessment and the European Regional Development Fund (ERDF). A.F.R., M.G.-F., M.G.-A., and M.A.J.-S. are supported by “Instituto de Salud Carlos III” (Grant Nos. UIPY-1377/08, RD12/0017/0024, CD12/00442, and CD13/00013, respectively). J.B. is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS).

A.F.R. and S.R. performed all statistical analysis, interpretation of the data, and wrote the manuscript. J.B., V.S., and S.R. participated in the study concept and design. J.B., V.S., J.C., J.C.L., and P.M. participated in patient selection, collection of samples, and acquisition of data. A.F.R., M.A.J.-S., M.G.-A., J.M.B., and N.R. participated in sample preparation, DNA isolation and genotyping preprocedure, and contributed with critical revision of the manuscript. S.R. supervised the study.

The authors have no conflicts of interest to disclose.

Received January 03, 2014

Accepted May 13, 2014

© 2014 by Lippincott Williams & Wilkins