A defect in the GCH1 gene, which encodes an essential protein for dopamine production in the brain, may accelerate the development of Parkinson’s disease, especially in people younger than 50, according to new research.
The study, “Aging Modifies The Effect Of GCH1 RS11158026 On DAT Uptake And Parkinson’s Disease Clinical Severity,” was published in the journal Neurobiology of Aging.
Rigidity and uncontrolled movements in patients with Parkinson’s disease are caused by the loss of neurons that produce dopamine in the brain. Mutations in genes that contribute to dopamine production can, therefore, speed up the onset of the disease and its symptoms. The identification of such genetic variations can be a useful diagnostic tool and help design personalized medical care for patients.
“We want to have a more comprehensive understanding of what these genes related to Parkinson’s are doing at different points in someone’s lifetime,” Auriel Willette, one of the study’s authors, said in a news release. “Then, with genetic testing we can determine the risk for illness based on someone’s age, gender, weight and other intervening factors.”
To study the influence of a mutation in the GCH1 gene, researchers followed a group of 289 newly diagnosed and untreated Caucasian Parkinson’s patients from the Parkinson’s Progression Markers Initiative, and 233 healthy individuals of the same age. They found that patients that carried this genetic variation were at higher risk of developing the disease (23 percent) and that symptoms appeared five years earlier than in other patients.
The GCH1 gene variation was also associated with lower levels of dopamine in the striatum (a brain area that is particularly affected in Parkinson’s); increased levels of alpha-synuclein (the protein that contributes to the pathology of the disease) in the cerebrospinal fluid; worse motor and executive function; and higher levels of anxiety.
Importantly, carriers of the variation who were younger than 50 had a 45 percent risk of developing the disease, whereas in older patients the variation had little effect. This result indicates that GCH1 variants influence the risk for early onset of Parkinson’s disease through changes in dopamine levels in the brain, and that age alters how genetic factors contribute to disease development.
“As we age, we progressively make less dopamine, and this effect strongly outweighs the genetic influences from the ‘bad version’ of this gene,” said Joseph Webb, the lead author of the study. “Simply by aging, our dopamine production decreases to the point that the effects from a mutation in this gene are not noticeable in older adults, but make a big difference in younger populations.”
According to the authors, cholesterol is an established risk factor for Parkinson’s and is directly related to the production of dopamine. They found that carriers of the GCH1 gene variation had higher blood cholesterol levels than other patients, regardless of their age.
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