对氧磷酶 1 基因单倍型与 HIV 感染患者的代谢紊乱、动脉粥样硬化和免疫结果相关。

Paraoxonase-1 gene haplotypes are associated with metabolic disturbances, atherosclerosis, and immunologic outcome in HIV-infected patients.

机构信息

Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Lleida, Spain.

出版信息

J Infect Dis. 2010 Feb 15;201(4):627-34. doi: 10.1086/650312.

DOI:10.1086/650312

PMID:20078196

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.

摘要

背景

氧化应激与人类免疫缺陷病毒（HIV）感染有关。对氧磷酶-1（PON1）是一种与高密度脂蛋白（HDL）结合的抗氧化酶。我们评估了 PON1 基因单倍型是否会影响与感染相关的代谢紊乱、亚临床动脉粥样硬化的发生和病毒学结果。

方法

使用 Iplex Gold MassArray 方法分析了来自 234 名 HIV 感染患者和 633 名健康对照者的血液样本中的 PON1(192)、PON1(55)、PON1(-162)、PON1(-832)、PON1(-909)、PON1(-1076)和 PON1(-1741)的单核苷酸多态性。随后，评估了这些单核苷酸多态性对测定的生化和临床变量的影响。

结果

我们观察到对照组和 HIV 感染患者之间的单倍型分布存在显著差异。HIV 感染患者中 H10 单倍型（GTCCGTC）更为常见（6.41%比 0.64%；P<0.001），而 H5 单倍型（GACCGTC）在 HIV 感染患者中更为少见（27.7%比 42.9%；P=0.001）。在 HIV 感染患者中，H7 单倍型（AATTCCT）与更好的 CD4(+)细胞计数恢复、更高水平的高密度脂蛋白胆固醇（P=0.048）和载脂蛋白 A-I（P=0.019）、更低水平的甘油三酯（P=0.004）以及更低的亚临床动脉粥样硬化发生率（P<0.001）相关。