The Functional Analysis of Selenium-Related Genes and Magnesium-Related Genes in the Gene Expression Profile Microarray in the Peripheral Blood Mononuclear Cells of Keshan Disease.

Abstract

Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) deficiency is closely related to KD, while magnesium (Mg) plays many critical roles in the cardiovascular function. The molecular mechanism of KD pathogenesis is still unclear. Until now, we have not found any studies investigating the association between Se- or Mg-related genes and KD. In this study, oligonucleotide microarray analysis was used to identify the differentially expressed genes in the peripheral blood mononuclear cells between KD patients and normal controls. Next, human metabolome database (HMDB) was used to screen Se- and Mg-related genes. Function classification, gene pathway, and interaction network of Se- and Mg-related genes in KD peripheral blood mononuclear cells were defined by FunRich (functional enrichment analysis tool). Among 83 differentially expressed genes, five Se-related (DIO2, GPX1, GPX2, GPX4, and GPX7) and five Mg-related (ACSL6, EYA4, IDH2, PPM1A, and STK11) genes were recognized from HMDB. Two significant biological processes (energy pathways and metabolism), one molecular function (peroxidase activity), one biological pathway (glutathione redox reactions I), and one gene interaction network were constituted from Se-related and Mg-related genes. Se-related gene DIO2 and Mg-related genes STK11 and IDH2 may have key roles in the myocardial dysfunction of KD. However, we still have not obtained any interaction between Se-related gene and Mg-related gene. The interactions between RPS6KB1, PTEN, ATM, HSP90AA1, SNRK, PRKAA2, SMARCA4, HSPA1A, and STK11 may play important roles in the abnormal cardiac function of KD.