Paraoxonase-1 gene haplotypes are associated with metabolic disturbances, atherosclerosis, and immunologic outcome in HIV-infected patients.
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.
Parra
Sandra
S
Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Lleida, Spain.
Marsillach
Judit
J
Aragonés
Gerard
G
Beltrán
Raúl
R
Montero
Manuel
M
Coll
Blai
B
Mackness
Bharti
B
Mackness
Michael
M
Alonso-Villaverde
Carlos
C
Joven
Jorge
J
Camps
Jordi
J
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
D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase