New Data Reveals 19 Genes Exhibit Expression Changes in HCV, Parkinson Disease

A new study has identified 19 genes, including MT1H, MY0M2, and RPL18, showing significant expression changes in both hepatitis C virus (HCV) infection and Parkinson Disease, suggesting a potential connection between the 2 conditions.¹

“…some gene expression changes frequently occurred in both sexes, but there were also gene expression changes unique to each sex,” wrote investigators, led by Isis Narvéez-Bandera, PhD, from the University of Puerto Rico-Mayagüez.

Over the last decade, researchers have found 90 risk alleles for Parkinson Disease, a condition that led to 5.8 million years of disability-adjusted life lost in 2019. However, only 20% of Parkinson Disease risk can be explained by these genes, leaving 80% unexplained. There’s evidence that bacterial or viral infections, like influenza, could increase the risk for sporadic Parkinson Disease.

HCV infection, like Parkinson Disease, also poses serious health risks. While some people clear the virus naturally, > 50% develop a chronic illness. Symptoms, often associated with advanced liver disease, include fatigue, jaundice, dark urine, swollen legs, and hepatic encephalopathy, among others, according to the Mayo Clinic.²

Earlier research has suggested a link between HCV infection and Parkinson Disease.¹ To further investigate this, the study aimed to uncover biomarkers and pathways potentially involved in both diseases.

The team analyzed 22 datasets (microarray and RNAseq) from patients with Parkinson Disease and HCV, totaling 1064 samples (Parkinson Disease: 6 microarrays and 2 RNAseq and HCV infection (12 microarrays and 2 RNAseq). They identified 367 genes related to Parkinson Disease and 418 genes associated with HCV infection, with 34 genes overlapping between the two diseases.

Of those, 19 genes showed significant expression changes in both conditions, including MT1H, MYOM2, S100A12, RPL18, IFIT1, SLC30A2, SAA1, LYZ, CEBPD, GPX3, SRGN, PGK1, SERPI1, FOS, GRN, GSTM1, CXCL1, KRT23, and EPB41L3.

The team observed the expression of MT1H, SLC30A2, KRT23, RPL18, IFIT1, and S100A12 were upregulated during HCV infection, while the expression of MYOM2 and GPX3 were downregulated. The gene INFIT1 plays a role in cGAS/STING immune pathway that the virus can block early on. However, in a chronic HCV infection, the host cells active this pathway as a defense mechanism, which could lead to inflammation.

The study suggests that prolonged inflammation caused by chronic HCV infection could lead to brain inflammation, increasing the risk of Parkinson Disease. Genes such as RPL18, KRT23, MT1H, and SLC30A also contribute to inflammation, oxidative stress, and neuron damage, potentially aiding HCV persistence and causing long-term damage that might lead to Parkinson Disease.

When analyzing gene expression by sex, the study found 604 genes linked to sex-related effects, with 470 genes showing changes unrelated to sex. MT1H was the most observed gene in both conditions. The analysis showed these gene expression changes were primarily linked to immune response regulation in females and immune cell activation in males.

“These results provide interesting leads for future experiments that could follow the role of each of these genes in a possible increase (or decrease) in the risk of developing [Parkinson Disease], and how these changes might help explain why HCV and [Parkinson Disease] affect males and females differently,” investigators wrote.

As for signaling pathways, a change in MST1 expression was strongly correlated with changes in the expression of the FOSL2, FOS, MMP9, and PRKCD genes. Additionally, changes in MST2 expression were strongly associated with changes in the expression of the SLC4A1 and EPB42 genes. CORO1A was also strongly correlated with changes in the expression of ARHGDIB.

“These findings suggest a potential link between HCV infection and [Parkinson Disease], highlighting the importance of further investigation into the underlying mechanisms and potential therapeutic targets involved,” investigators concluded.

References

1. ^{Narváez-Bandera I, Suárez-Gómez D, Castro-Rivera CDM, et al. Hepatitis C virus infection and Parkinson's disease: insights from a joint sex-stratified BioOptimatics meta-analysis. Sci Rep. 2024;14(1):22838. Published 2024 Oct 1. doi:10.1038/s41598-024-73535-0}
2. ^{Hepatitis C. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/hepatitis-c/symptoms-causes/syc-20354278. Accessed October 21, 2024.}