title: Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS).
abstract: OBJECTIVE
  A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS.
  
  
  METHODS
  This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis.
  
  
  RESULTS
  LBP rs2232582 T→C polymorphism was significantly associated with HALS (P = 0.01 and P = 0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (P = 0.009) and LBP (P < 0.001) were significantly higher and sCD14 significantly lower (P < 0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (P < 0.001) and hepatitis C virus (P = 0.038), LBP levels by HALS (P < 0.001) and sCD14 levels by age (P = 0.008), current HIV-1 viral load (P = 0.001) and protease inhibitor use (P = 0.018).
  
  
  CONCLUSIONS
  HALS is associated with LBP polymorphism and with higher bacterial translocation.
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Viladés
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Tarragona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Escoté
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Dupla
authors.affiliation: Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Martinez
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Hospital General de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Asensi
authors.affiliation: Laboratorio de Inmunovirologia, Unidad de Gestión Clínica de Enfermedades Infecciosas, Microbiologia y Medicina Preventiva, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Peraire
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Inza
authors.affiliation: Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Arnedo
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Gutiérrez
authors.affiliation: Hospital General de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Valle-Garay
authors.affiliation: Laboratorio de Inmunovirologia, Unidad de Gestión Clínica de Enfermedades Infecciosas, Microbiologia y Medicina Preventiva, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain Laboratorio de Inmunobiologia Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBER de Bioingeniaria, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martinez
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Olona
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Alba
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Joan-Josep
authors.initials: JJ
authors.lastname: Sirvent
authors.affiliation: Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain fvidalmarsal.hj23.ics@gencat.cat.
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012307:Risk Factors; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D051197:Toll-Like Receptor 4; D000099231:Lipopolysaccharide-Binding Protein
keywords: genetics; inflammation; microbial translocation