title: Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.
abstract: BACKGROUND
  Interleukin-7 (IL-7) is a critical factor for T cell development and for maintaining and restoring homeostasis of mature T cells. Polymorphisms at α-chain of the IL-7 receptor (IL7R or CD127) gene are related to evolution of HIV-infection, but there are no data concerning the evolution of hepatitis C virus (HCV) infection. The aim of this study was to analyze the association between IL7R polymorphisms and severe liver disease in HCV/HIV coinfected patients.
  
  
  METHODS
  We performed a cross-sectional study in 220 naïve patients who underwent a liver biopsy. IL7R polymorphisms (rs6897932, rs987106 and rs3194051) were genotyped using the GoldenGate(®) assay. The outcome variables were: (a) liver biopsy: advanced fibrosis (F ≥ 3), severe activity grade (A3); (b) non-invasive indexes: advanced fibrosis (APRI ≥1.5 and FIB-4 ≥3.25). Logistic regression analysis was used to investigate the association between IL7R polymorphisms and outcome variables. This test gives the differences between groups and the odds ratio (OR) for liver disease.
  
  
  RESULTS
  Patients with rs6897932 CC genotype had higher likelihood of having A3 than patients with rs6897932 CT/TT (adjusted odds ratio (aOR) = 4.16; p = 0.026). Patients with rs987106 TT genotype had higher odds of having F ≥ 3 (aOR = 3.09; p = 0.009) than rs987106 AA/AT carriers. Finally, patients with rs3194051 AA genotype had higher odds of having severe liver fibrosis (F ≥ 3; APRI ≥1.5, and FIB4 ≥3.25) than patients with rs3194051 AG/GG genotype [aOR = 2.73 (p = 0.010); aOR = 2.52 (p = 0.029); and aOR = 4.01 (p = 0.027); respectively]. The CTA haplotype (comprised of rs6897932, rs987106, and rs3194051) carriers had higher odds of having F ≥ 3 (aOR = 1.85; p = 0.012), APRI ≥1.5 (aOR = 1.94; p = 0.023), and FIB4 ≥3.25 (aOR = 2.47; p = 0.024). Conversely, the CAG haplotype carriers had lower odds of having F ≥ 3 (aOR = 0.48; p = 0.011), APRI ≥1.5 (aOR = 0.48; p = 0.029), and FIB4 ≥3.25 (aOR = 0.29; p = 0.010).
  
  
  CONCLUSIONS
  The presence of IL7R polymorphisms seems to be related to severe liver disease in HIV/HCV coinfected patients, because patients with unfavorable IL7R genotypes (rs6897932 CC, rs987106 TT, and rs3194051AA) had a worse prognosis of CHC.
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. m22guzman@gmail.com.
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain. jberenguer.hgugm@salud.madrid.org.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. jberenguer.hgugm@salud.madrid.org.
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. jimenezsousa@isciii.es.
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. dpineda@isciii.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain. teresaldamiz@yahoo.es.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. teresaldamiz@yahoo.es.
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarria
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. pgarciabroncano@gmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Broncano
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain. ana_carrero@yahoo.es.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. ana_carrero@yahoo.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Carrero
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. monica_gap@yahoo.es.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain. pacotejerina@gmail.com.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. pacotejerina@gmail.com.
authors.forename: Francisco
authors.initials: F
authors.lastname: Tejerina
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain. crispu82@gmail.com.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. crispu82@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Diez
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. svazquez@isciii.es.
authors.forename: Sonia
authors.initials: S
authors.lastname: Vazquez-Morón
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, Majadahonda, 28220, Madrid, Spain. sresino@isciii.es.
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D060085:Coinfection / Q000150:complications / Q000235:genetics* / Q000821:virology; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006678:HIV; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D006239:Haplotypes / Q000235:genetics; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020395:Receptors, Interleukin-7 / Q000235:genetics*
chemical_list: D020395:Receptors, Interleukin-7