Anyona Samuel B, Raballah Evans, Cheng Qiuying, Hurwitz Ivy, Ndege Caroline, Munde Elly, Otieno Walter, Seidenberg Philip D, Schneider Kristan A, Lambert Christophe G, McMahon Benjamin H, Ouma Collins, Perkins Douglas J
Department of Medical Biochemistry, School of Medicine, Maseno University, Maseno, Kenya.
University of New Mexico-Kenya Global Health Programs, Kisumu and Siaya, Kenya.
Front Genet. 2021 Nov 22;12:764759. doi: 10.3389/fgene.2021.764759. eCollection 2021.
Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored. To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children ( = 44, aged <48 mos) with either mild malarial anemia (MMA; Hb ≥9.0 g/dl; = 23) or SMA (Hb <6.0 g/dl; = 21) using the Qiagen Human Ubiquitination Pathway RT Profiler PCR Array containing a set of 84 human ubiquitination genes. In children with SMA, 10 genes were down-regulated (, , , , , , , , , ), and five genes were up-regulated (, , , , ). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process, along with altered sub-networks involved in proteasomal, protein, and ubiquitin-dependent catabolic processes. Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA.
疟疾仍然是全球儿童发病和死亡的主要原因之一。在高度流行传播地区，如肯尼亚西部，严重疟疾贫血（SMA，血红蛋白（Hb）<6.0 g/dl）是严重疾病的主要形式。泛素化对于调节先天免疫和适应性免疫中涉及的细胞内过程至关重要。虽然泛素分子过程的失调是多种人类疾病发病机制的核心，但SMA中泛素化基因的表达模式仍未得到探索。为了研究泛素化过程在SMA发病机制中的作用，使用包含一组84个人类泛素化基因的Qiagen人类泛素化途径RT Profiler PCR阵列，在患有轻度疟疾贫血（MMA；Hb≥9.0 g/dl；n = 23）或SMA（Hb<6.0 g/dl；n = 21）的肯尼亚儿童（n = 44，年龄<48个月）中确定了差异基因表达谱。在患有SMA的儿童中，10个基因下调（……），5个基因上调（……）。富集分析显示泛素-蛋白酶体蛋白水解是最受干扰的过程，同时涉及蛋白酶体、蛋白质和泛素依赖性分解代谢过程的子网络也发生了改变。总的来说，这些新结果表明泛素化过程的蛋白质编码基因参与了SMA的发病机制。
