2026-06-30T03:49:41Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/48242025-04-03T17:25:31Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16978
Repisalud author Pineda-Tenor, Daniel author Berenguer, Juan author Jimenez-Sousa, Maria Angeles author Garcia-Alvarez, Monica author Aldámiz-Echevarria, Teresa author Carrero, Ana author Vázquez-Morón, Sonia author Garcia-Broncano, Pilar author Díez, Cristina author Tejerina, Francisco author Guzman-Fulgencio, Maria author Resino, Salvador funder Instituto de Salud Carlos III funder Fundación para la Investigación y la Prevención del Sida en España funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 2017-09-04T16:30:19Z 2017-09-04T16:30:19Z 2014-11-03 BMC Med. 2014; 12: 198. 10.1186/s12916-014-0198-y 1741-7015 BMC Medicine 25367448 http://hdl.handle.net/20.500.12105/4824 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. eng AIDS Chronic hepatitis C HCV therapy Metabolism Insulin resistance Obesity SNPs FTOrs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients research article URL https://repisalud.isciii.es/bitstreams/b79492e8-0bd6-4d73-a2a1-33f4b8b44971/download File MD5 a875b30f39d25345e0d16b12d29fe06d 1297251 application/pdf FTORs9939609PolymorphismIs_2014.pdf URL https://repisalud.isciii.es/bitstreams/4f2111c8-75fe-468b-bd55-c9e05fe2eee4/download File MD5 125f18a268773d5720db197a00b79b00 57356 text/plain 12916_2014_Article_198.pdf.txt URL https://repisalud.isciii.es/bitstreams/e62e2b77-4b71-4ff9-8146-724648886c89/download File MD5 125f18a268773d5720db197a00b79b00 57356 text/plain 12916_2014_Article_198.pdf.txt URL https://repisalud.isciii.es/bitstreams/4127fc75-7c29-47aa-9bbe-09e193de7fba/download File MD5 125f18a268773d5720db197a00b79b00 57356 text/plain FTORs9939609PolymorphismIs_2014.pdf.txt URL https://repisalud.isciii.es/bitstreams/36d03769-60c6-4581-9aee-42394973c46b/download File MD5 2dfda9fc67643f1c21202e2951bde88f 57315 text/plain FTORs9939609PolymorphismIs_2014.pdf.txt