title: Relationship of TRIM5 and TRIM22 polymorphisms with liver disease and HCV clearance after antiviral therapy in HIV/HCV coinfected patients.
abstract: TRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients.
  
  
  
  A retrospective study was performed in 319 patients who started pegIFNα/RBV therapy. Liver fibrosis stage was characterized in 288 patients. TRIM5 rs3824949 and TRIM22 polymorphisms (rs1063303, rs7935564, and rs7113258) were genotyped using the GoldenGate assay. The primary outcomes were: a) significant liver fibrosis (≥F2) evaluated by liver biopsy or transient elastography (liver stiffness values ≥7.1 Kpa); b) sustained virological response (SVR) defined as no detectable HCV viral load (<10 IU/mL) at week 24 after the end of the treatment. The secondary outcome variable was plasma chemokine levels.
  
  
  
  Patients with TRIM5 rs3824949 GG genotype had higher SVR rate than patients with TRIM5 rs3824949 CC/CG genotypes (p = 0.013), and they had increased odds of achieving SVR (adjusted odds ratio (aOR = 2.58; p = 0.012). Patients with TRIM22 rs1063303 GG genotype had higher proportion of significant liver fibrosis than patients with rs1063303 CC/CG genotypes (p = 0.021), and they had increased odds of having significant hepatic fibrosis (aOR = 2.19; p = 0.034). Patients with TRIM22 rs7113258 AT/AA genotype had higher SVR rate than patients with rs7113258 TT genotypes (p = 0.013), and they had increased odds of achieving SVR (aOR = 1.88; p = 0.041). The TRIM22 haplotype conformed by rs1063303_C and rs7113258_A was more frequent in patients with SVR (p = 0.018) and was significantly associated with achieving SVR (aOR = 2.80; p = 0.013). The TRIM5 rs3824949 GG genotype was significantly associated with higher levels of GRO-α (adjusted arithmetic mean ratio ((aAMR) = 1.40; p = 0.011) and MCP-1 (aAMR = 1.61; p = 0.003).
  
  
  
  TRIM5 and TRIM22 SNPs are associated to increased odds of significant liver fibrosis and SVR after pegIFNα/RBV therapy in HIV/HCV coinfected patients. Besides, TRIM5 SNP was associated to higher baseline levels of circulating biomarkers GRO and MCP-1.
authors: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors: Luz M
authors: LM
authors: Medrano
authors: Instituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
authors: Norma
authors: N
authors: Rallón
authors: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors: Juan
authors: J
authors: Berenguer
authors: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors: María A
authors: MA
authors: Jiménez-Sousa
authors: Unidad de Enfermedades Infecciosas, Hospital Universitario La Paz, Madrid, Spain.
authors: Vicente
authors: V
authors: Soriano
authors: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors: Teresa
authors: T
authors: Aldámiz-Echevarria
authors: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors: Amanda
authors: A
authors: Fernández-Rodríguez
authors: Instituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
authors: Marcial
authors: M
authors: García
authors: Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors: Francisco
authors: F
authors: Tejerina
authors: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors: Isidoro
authors: I
authors: Martínez
authors: Instituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
authors: José M
authors: JM
authors: Benito
authors: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain. sresino@isciii.es.
authors: Salvador
authors: 0000-0001-8783-0450
authors: S
authors: Resino
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics*; D018925:Chemokines / Q000097:blood; D060085:Coinfection / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D000070584:Tripartite Motif Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D000998:Antiviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D018925:Chemokines; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: AIDS; Fibrosis; HCV therapy; SNPs; TRIM22; TRIM5