Pérez-Matute Patricia, Iñiguez María, Recio-Fernández Emma, Oteo José-Antonio
HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR)-Hospital San Pedro, Piqueras 98, 26006, Logroño, Spain.
Genomics Core Facility, Center for Biomedical Research of La Rioja (CIBIR), Piqueras 98, 26006, Logroño, Spain.
J Physiol Biochem. 2016 Aug;73(3):431-443. doi: 10.1007/s13105-016-0547-8. Epub 2017 Jan 10.
HIV-associated lipoatrophy (LA) has considerable implications for risk of metabolic diseases, quality of life, and adherence to treatments. Although it has decreased in high-income countries, it is still very common in resource-limited countries. Understanding the pathophysiological mechanisms of LA can open the possibility to explore new ways to treat or prevent this condition. To identify new markers for an accurate and quick diagnosis will be also of interest. Thus, we aimed to examine functional classes of genes implicated in LA and to identify potential new markers for an accurate/quick diagnosis of LA and future complications. Eighteen participants were recruited: seven healthy volunteers, five non-LA-HIV patients, and six LA-HIV subjects. Clinical lipoatrophy was considered when changes in fat volume in the cheeks next to the nose, lateral aspect of the face, legs, arms, and buttocks were observed by the physicians. mRNA was isolated from peripheral blood mononuclear cells (PBMCs) to perform a transcriptomic and Gene Ontology analysis. To confirm RNA sequencing results, qPCRs were developed. A total of 55 genes were differentially expressed between LA and non-LA patients. Thirty-seven genes were overexpressed, whereas 18 genes were repressed. Functional analysis showed that overexpressed genes were involved in lymphocyte/neutrophil activation, inflammation, and atherogenesis. Several lymphoma markers and members of the lipocalin and aquaporin families were also found more expressed in LA patients. In contrast, most of the genes found less expressed in LA subjects were involved in angiogenesis and protection against myocardial infarction. Our results demonstrated a distinct transcriptomic signature in PBMCs of LA patients in comparison with non-LA-HIV subjects and, therefore, provided novel insights to the pathogenesis of HIV-associated lipoatrophy. Our study also highlights the potential usage of some of these genes as early markers of future complications.
与HIV相关的脂肪萎缩（LA）对代谢性疾病风险、生活质量以及治疗依从性具有重大影响。尽管在高收入国家其发生率有所下降，但在资源有限的国家仍然非常普遍。了解LA的病理生理机制有助于探索治疗或预防这种病症的新方法。识别用于准确快速诊断的新标志物也将具有重要意义。因此，我们旨在研究与LA相关的基因功能类别，并识别用于准确/快速诊断LA及未来并发症的潜在新标志物。招募了18名参与者：7名健康志愿者、5名无LA的HIV患者和6名有LA的HIV受试者。当医生观察到鼻子旁脸颊、面部侧面、腿部、手臂和臀部的脂肪体积发生变化时，即认为存在临床脂肪萎缩。从外周血单核细胞（PBMC）中分离mRNA以进行转录组学和基因本体分析。为了确认RNA测序结果，开展了定量聚合酶链反应（qPCR）。LA患者和无LA患者之间共有55个基因差异表达。37个基因过度表达，而18个基因表达受抑制。功能分析表明，过度表达的基因参与淋巴细胞/中性粒细胞活化、炎症和动脉粥样硬化形成。还发现几种淋巴瘤标志物以及脂质运载蛋白和水通道蛋白家族的成员在LA患者中表达更高。相比之下，在LA受试者中表达较低的大多数基因参与血管生成和心肌梗死保护。我们的结果表明，与无LA的HIV受试者相比，LA患者的PBMC具有独特的转录组特征，因此为HIV相关脂肪萎缩的发病机制提供了新见解。我们的研究还强调了其中一些基因作为未来并发症早期标志物的潜在用途。
