Paraoxonase-1 Gene Haplotypes Are Associated with Metabolic Disturbances

Identifier:  imarina:9297747

Handle: https://hdl.handle.net/20.500.11797/imarina9297747

Authors:  Parra, Sandra; Marsillach, Judit; Aragones, Gerard; Beltran, Raul; Montero, Manuel; Coll, Blai; Mackness, Bharti; Mackness, Michael; Alonso-Villaverde, Carlos; Joven, Jorge; Camps, Jordi

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.