Associations of the Methylation Levels of <b><i>NFAT5</i></b>, <b><i>PVT1</i></b>, <b><i>RPS6KA1</i></b>, and <b><i>MIB1</i></b> with Steroid-Resistant Asthma

Abstract

<b><i>Background:</i></b> This study detected the methylation levels of nuclear factor-5 <i>(NFAT5)</i>, <i>PVT1</i>, ribosomal protein S6 kinase A-1 (<i>RPS6KA1</i>), and <i>MIB1</i> in patients with steroid-resistant asthma (SRA) and explored their associations with SRA. <b><i>Methods:</i></b> In our pilot study, we found abnormal methylation of <i>NFAT5</i>, <i>PVT1</i>, <i>RPS6KA1,</i> and <i>MIB1</i> in SRA patients according to genome-wide methylation screening. This study expanded the sample size to further validate the results of the pilot study. Twenty patients with SRA, 20 patients with bronchial asthma, and 20 healthy volunteers constituted the SRA group, asthma control group, and healthy control group, respectively. The clinical data of all the participants were collected. Peripheral blood was taken for DNA extraction. The methylation loci and levels of <i>NFAT5</i>, <i>PVT1</i>, <i>RPS6KA1,</i> and <i>MIB1</i> were detected using the Sequenom MassARRAY Nanodispenser RS1000. Data were processed and analyzed with SPSS 22.0 software. <b><i>Results:</i></b> There were 24 CpG loci detected in the <i>NFAT5</i> segment 7 in the <i>PVT1</i> segment, 4 in the <i>RPS6KA1</i> segment, and 3 in the <i>MIB1</i> segment. Among these genes, RPS6KA exhibited hypomethylation in the SRA group, which showed significant differences at the CpG_1, CpG_2, and CpG_3 loci compared with the other groups (<i>p</i> &#x3c; 0.05). No significant differences in the methylation levels of <i>NFAT5</i>, <i>PVT1</i>, and <i>MIB1</i> were observed among the groups (<i>p</i> &#x3e; 0.05). <b><i>Conclusions:</i></b> <i>RPS6KA1</i> is hypomethylated in SRA patients, which may play a role in the development of SRA via the MAPK signaling pathway. However, the influence of the methylation of <i>NFAT5</i>, <i>PVT1,</i> and <i>MIB1</i> on SRA development remains to be explored.