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: Sandra Parra, Judit Marsillach, Gerard Aragonés, Raúl Beltrán, Manuel Montero, Blai Coll, Bharti Mackness, Michael Mackness, Carlos Alonso-Villaverde, Jorge Joven, Jordi Camps
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 201 Issue 4 Pg. 627-34 (Feb 15 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20078196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins, HDL
• Aryldialkylphosphatase

Topics

• Adult
• Aged
• Aged, 80 and over
• Aryldialkylphosphatase (genetics)
• Atherosclerosis (enzymology, genetics)
• CD4 Lymphocyte Count
• Case-Control Studies
• Female
• HIV Infections (enzymology, genetics, immunology)
• Haplotypes
• Humans
• Kaplan-Meier Estimate
• Linear Models
• Linkage Disequilibrium
• Lipoproteins, HDL (metabolism)
• Male
• Metabolic Diseases (enzymology, genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors