Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina.
PLoS One. 2012;7(7):e39678. doi: 10.1371/journal.pone.0039678. Epub 2012 Jul 25.
Polymorphisms in apolipoprotein genes have shown to be predictors of plasma lipid levels in adult cohorts receiving highly active antiretroviral therapy (HAART). Our objective was to confirm the association between the APOC3 genotype and plasma lipid levels in an HIV-1-infected pediatric cohort exposed to HAART. A total of 130 HIV-1-infected children/adolescents that attended a reference center in Argentina were selected for an 8-year longitudinal study with retrospective data collection. Longitudinal measurements of plasma triglycerides, total cholesterol, HDL-C and LDL-C were analyzed under linear or generalized linear mixed models. The contribution of the APOC3 genotype at sites -482, -455 and 3238 to plasma lipid levels prediction was tested after adjusting for potential confounders. Four major APOC3 haplotypes were observed for sites -482/-455/3238, with estimated frequencies of 0.60 (C/T/C), 0.14 (T/C/C), 0.11 (C/C/C), and 0.11 (T/C/G). The APOC3 genotype showed a significant effect only for the prediction of total cholesterol levels (p<0.0001). However, the magnitude of the differences observed was dependent on the drug combination (p = 0.0007) and the drug exposure duration at the time of the plasma lipid measurement (p = 0.0002). A lower risk of hypercholesterolemia was predicted for double and triple heterozygous individuals, mainly at the first few months after the initiation of Ritonavir-boosted protease inhibitor-based regimens. We report for the first time a significant contribution of the genotype to total cholesterol levels in a pediatric cohort under HAART. The genetic determination of APOC3 might have an impact on a large portion of HIV-1-infected children at the time of choosing the treatment regimens or on the counter-measures against the adverse effects of drugs.
载脂蛋白基因多态性已被证明可预测接受高效抗逆转录病毒疗法（HAART）的成年队列中的血浆脂质水平。我们的目的是在接受 HAART 的 HIV-1 感染儿科队列中确认 APOC3 基因型与血浆脂质水平之间的关联。总共选择了 130 名在阿根廷参考中心就诊的 HIV-1 感染儿童/青少年进行了 8 年的纵向研究，并进行了回顾性数据收集。在调整潜在混杂因素后，分析了线性或广义线性混合模型下血浆甘油三酯、总胆固醇、HDL-C 和 LDL-C 的纵向测量值。在调整潜在混杂因素后，测试了 APOC3 基因型在 -482、-455 和 3238 位点对血浆脂质水平预测的贡献。在 -482/-455/3238 位点观察到四个主要的 APOC3 单倍型，估计频率分别为 0.60（C/T/C）、0.14（T/C/C）、0.11（C/C/C）和 0.11（T/C/G）。APOC3 基因型仅对总胆固醇水平的预测有显著影响（p<0.0001）。然而，观察到的差异幅度取决于药物组合（p=0.0007）和血浆脂质测量时的药物暴露时间（p=0.0002）。双和三重杂合子个体发生高胆固醇血症的风险较低，主要在开始利托那韦增效蛋白酶抑制剂为基础的方案后的前几个月。我们首次报告了在接受 HAART 的儿科队列中，基因型对总胆固醇水平有显著影响。APOC3 的遗传决定因素可能会对接受治疗方案时的大部分 HIV-1 感染儿童产生影响，或者对药物不良反应的对策产生影响。
