177 - The Role of the HNRNPH2 Gene in Fabry Disease-related Pain

Fabry disease (FD) is a rare X-linked genetic lysosomal storage disease with a worldwide prevalence of one in 60000 males. Patients with FD can suffer from severe pain, gastrointestinal problems, and death due to kidney or heart failure. FD is often caused by a mutation of the α-galactosidase A (GLA) gene, which can lead to the accumulation of globotriaosylceramide (Gb3) in cells and tissues. The deposition of Gb3 in ganglions and nerves is associated with neurological pain among patients suffering from FD. Unmanaged pain can have detrimental effects on one’s quality of life, and, unfortunately, current FD therapies fall short when treating FD-related pain. Thus, exploring therapeutic targets to alleviate FD-related pain is an important research topic. One of the possible therapeutic targets is the HNRNPH2 gene, which is located on the opposite strand of GLA and plays an essential role in the development of pain-related neurological disorders.

Objective:

To establish the role of the HNRNPH2 gene in FD-related pain for future studies focusing on therapeutic targets for FD-related pain.

Design/Methods:

The FD (three female and three male) and fibroblast-derived control cell lines were purchased from Cornell Institute for Medical Research and grew as per supplier instruction. The harvested cell mRNA expression was analyzed using qRT-PCR. The gene expression analysis and gene expression correlation were done by Omics Playground cloud base software using the Spearman correlation statistical algorithm. A correlation value >0.3 was considered clinically significant for candidate gene(s). The gene expression dataset was obtained from Gene Expression Omnibus GEO (GSE110645, GSE112895, and GSE164941). Gene public datasets were obtained from multiple public databases.

Results:

Our gene expression analysis showed co-down regulation of HNRNPH2 and GLA genes in 5 of 6 FD-derived cell lines. Unexpectedly, GLA had more reduction in expression in female than male cell lines. The reduced expression of the genes was also observed in FD mouse and human kidney organoid data sets. The alteration of the HNRNPH2 gene correlated with 19 consensus pain gene sets obtained from five public data sets.

Conclusion(s):

Our study concluded that alteration in GLA in FD patients affects the expression of the HNRNPH2 gene, which likely plays a role in pain network gene regulation and contributes to FD-related pain.