title: Single nucleotide polymorphisms of CXCL9-11 chemokines are associated with liver fibrosis in HIV/HCV-coinfected patients.
abstract: BACKGROUND
  CXCR3A-associated chemokines (CXCL9-11) are implicated in the pathogenesis of hepatitis C virus (HCV) infection. We analyzed the association between CXCL9-11 polymorphisms and significant liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients.
  
  
  METHODS
  We performed a cross-sectional study in 220 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using GoldenGate assay. Three outcome variables related to liver fibrosis were studied: (1) F ≥ 2; (2) APRI ≥ 2; and (3) FIB-4 ≥ 3.25.
  
  
  RESULTS
  The percentage of patients with significant liver fibrosis (F ≥ 2, APRI ≥ 2, and FIB-4 ≥ 3.25) was significantly higher for CXCL9 rs10336 TT (P = 0.046, P = 0.010, and P = 0.046, respectively), CXCL10 rs3921 GG (P = 0.046, P = 0.011, and P = 0.049, respectively), and CXCL11 rs4619915 AA (P = 0.035, P = 0.014, and P = 0.057, respectively) genotypes. Moreover, the greater likelihood of having significant liver fibrosis (F ≥ 2, APRI ≥ 2, and FIB-4 ≥ 3.25) was found in carriers of CXCL9 rs10336 TT and CXCL10 rs3921 GG [adjusted odds ratio (aOR) > 2 (P < 0.05)]. These trends were significantly more pronounced in patients infected with HCV-genotype 1 (GT1) [aOR > 3 (P < 0.05)]. Moreover, TGA haplotype showed higher odds for having values of APRI ≥ 2 (aOR = 2.4; P = 0.012) when we considered all patients. This elevated risk for significant liver fibrosis was better represented in patients infected with HCV-GT1, where TGA haplotype had increased odds for having values of F ≥ 2 (aOR = 1.9; P = 0.045), APRI ≥ 2 (aOR = 3.2; P = 0.009), and FIB-4 ≥ 3.25 (aOR = 3.3; P = 0.026).
  
  
  CONCLUSIONS
  The homozygosity for the minor alleles CXCL9 rs10336 (T), CXCL10 rs3921 (G), and CXCL11 rs4619915 (A) is associated with the higher likelihood of significant liver fibrosis in HIV-infected patients coinfected with HCV-GT1.
authors.affiliation: *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; and §Laboratorio de Inmunobiología Molecular, Hospital General Universitario "Gregorio Marañón," Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Ana
authors.initials: A
authors.lastname: Carrero
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarria
authors.forename: Francisco
authors.initials: F
authors.lastname: Tejerina
authors.forename: Cristina
authors.initials: C
authors.lastname: Diez
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: María A
authors.initials: MA
authors.lastname: Munoz-Fernandez
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D054371:Chemokine CXCL11 / Q000235:genetics*; D054370:Chemokine CXCL9 / Q000235:genetics*; D060085:Coinfection / Q000150:complications; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D060005:Genotyping Techniques; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006720:Homozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9