To detect potential pathways and target genes in infantile Pompe patients using computational analysis Bioimpacts.

2022;12(2):89-105. doi: 10.34172/bi.2022.23467.

PMID: 35411297

Aynur Karadağ Gürel, Selçuk Gürel

Highlights: In this study, the determination of key genes involved in the response to ERT for Pompe disease and potential molecular mechanisms were investigated.

Abstract

Introduction: Pompe disease (PD), also known as glycogen storage disease type II, is a condition marked by cardiac hypertrophy, respiratory failure, and muscle hypotonia that, if left untreated, can result in premature mortality. It is brought on by pathogenic mutations in the GAA gene. Enzyme replacement therapy (ERT), the only available treatment, greatly improves the prognosis for some individuals while failing to assist others. In this study, potential molecular pathways and the identification of important genes implicated in the response to ERT were examined.

Methods: It was done using Gene Expression Omnibus (GEO) data with the accession number GSE38680, which contained samples of the quadriceps and biceps muscles. BRB-Array Tools were used to examine expression array data. Patients in the quadriceps group got therapy with rhGAA at 0, 12, and 52 weeks while those in the biceps group did not get ERT. Differentially expressed genes (DEGs) were thoroughly examined using the online analysis DAVID, GO, KEGG, and STRING, respectively.

Results: In total, 1198 genes in the quadriceps group and 1727 genes in the biceps group have different expression patterns. In the group that responded poorly to ERT in the 52nd week, it was found that DEGs were enriched. The expression of 530 genes increased and 1245 genes decreased in comparison to 0 and 12 weeks in the weak response group, which experienced frequent gene changes. According to the GO analysis, the DEGs were primarily involved in the contraction of vascular smooth muscle, lysosomes, autophagy, actin cytoskeleton regulation, inflammatory response, and the WNT signaling pathway. It is also found that DEGs and the WNT signaling pathway had a strong correlation. A number of DEGs, including WNT11, WNT5A, CTNNB1, M6PR, MYL12A, VCL, TLN, FYN, YES1, and BCL2, might be crucial in illuminating the processes behind a poor response to ERT.

Conclusion: For the treatment of the disease, early PD diagnosis and treatment are crucial. As a result, it implies that the analysis's enriched genes and newly discovered pathways may be used to determine whether patients respond poorly to treatment and how well they respond to it. Neonatal screening results will help with diagnosis and treatment by revealing genes and pathways.

Keywords: Bioinformatics, GAA gene, enzyme replacement therapy, GEO data, Pompe Disease, WNT signaling pathway