Scientists have identified a gene that can significantly increase the risk of Parkinson's disease. Although most of us generally carry the same genes, there may be small variations in the sequences of those genes, and those variations can sometimes have major biological effects. In this case, variants in a gene called ITSN1 can dramatically increase a carrier's risk of Parkinson's disease. The findings have been published in Cell Reports.
Parkinson's disease is a serious neurodegnerative disease that is thought to affect about 6 million people worldwide. The incidence of the disease is expected to rise. The symptoms of the disease include fatigue, depression, uncontrollable movements such as tremors or shaking, and behavioral changes. These symptoms arise when dopamine-producing neurons in a region of the brain called the basal ganglia begin to die off. Scientists are still trying to determine what causes these neurons to die.
In this work, the researchers used human genetic data from the UK Biobank to identify these Parkinson's linked variants in the ITSN1 gene. The research showed that rare ITSN1 variants disrupt the normal function of the gene, and can make a person's risk of Parkinson's disease as much as ten times higher than those who do not carry those variants.
These findings were then validated in three other large sets of human genetic data. Carriers of ITSN1 variants were also found to have an earlier average age of onset of Parkinson's compared to others with the disorder.
"What makes this discovery so significant is the exceptional magnitude of the effect of ITSN1 in increasing Parkinson's risk, especially when compared with variants in other well-established genes such as LRRK2 and GBA1," said co-corresponding study author Dr. Ryan S. Dhindsa, an assistant professor at Baylor College of Medicine, among other appointments.
The protein encoded by the ITSN1 plays a critical role in a neuronal communication process known as synaptic transmission.
This research team has used a fruit fly model to show that reductions in ITSN1 levels make Parkinson's disease symptoms worse. Now, Dhindsa said that the scientists want to follow up in this work in other models, such as stem cells and mice.
These findings coincide with other research studies that have shown that ITSN1 variants may also raise the risk of autism spectrum disorder. ASD patients are about three times more likely to develop Parkinson's disease than unaffected individuals, so this may represent a potential explanation for that observation.
"Our findings support future studies to better understand the connections between these two conditions and the mechanisms involved," Dhindsa said. This work also highlights how rare genetic variants can provide crucial insights into the mechanisms that drive disease, and open up potential new treatment options, added Dhindsa.
Sources: Baylor College of Medicine, Cell Reports