title: Paraoxonase-1 gene haplotypes are associated with metabolic disturbances, atherosclerosis, and immunologic outcome in HIV-infected patients.
abstract: BACKGROUND
  Oxidative stress is associated with human immunodeficiency virus (HIV) infection. Paraoxonase-1 (PON1) is an antioxidant enzyme that is bound to high-density lipoproteins (HDLs). We evaluated whether PON1 gene haplotypes influence the metabolic disturbances, presence of subclinical atherosclerosis, and virologic outcome associated with the infection.
  
  
  METHODS
  DNA from blood samples collected from 234 HIV-infected patients and 633 healthy control subjects had single-nucleotide polymorphisms of PON1(192), PON1(55), PON1(-162), PON1(-832), PON1(-909), PON1(-1076), and PON1(-1741) analyzed using the Iplex Gold MassArray method. Subsequently, the influence of these single-nucleotide polymorphisms on measured biochemical and clinical variables was assessed.
  
  
  RESULTS
  We observed significant differences in the haplotype distribution between the control subjects and the HIV-infected patients. Haplotype H10 (GTCCGTC) was more prevalent in the HIV-infected patients (6.41% vs 0.64%; P < .001), and haplotype H5 (GACCGTC) was less prevalent in HIV-infected patients (27.7% vs 42.9%; P = .001). In HIV-infected patients, haplotype H7 (AATTCCT) was associated with better CD4(+) cell count recovery, higher levels of HDL cholesterol (P = .048) and apolipoprotein A-I (P = .019), lower levels of triglycerides (P = .004), and lower rates of subclinical arteriosclerosis (P < .001).
  
  
  CONCLUSIONS
  PON1 haplotypes segregate with HIV infection, HDL metabolism, the presence of subclinical atherosclerosis, and CD4(+) cell recovery after treatment.
authors.affiliation: Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Lleida, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Parra
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonés
authors.forename: Raúl
authors.initials: R
authors.lastname: Beltrán
authors.forename: Manuel
authors.initials: M
authors.lastname: Montero
authors.forename: Blai
authors.initials: B
authors.lastname: Coll
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Michael
authors.initials: M
authors.lastname: Mackness
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso-Villaverde
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics*; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D015810:Linkage Disequilibrium; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase