A defect in a gene that produces dopamine in nigrostriatal cells appears to accelerate the onset of Parkinson’s disease, according to a study published in the February issue of Neurobiology of Aging. The effect is particularly pronounced for people younger than 50.
Auriel Willette, PhD, an Assistant Professor in the Departments of Food Science and Human Nutrition and Psychology at Iowa State University in Ames, and Joseph Webb, a graduate research assistant also at Iowa State, found on average that Caucasians with one mutated version of the gene—guanosine triphosphate cyclohydrolase-1 (GCH1)—had a 23% increased risk for Parkinson’s disease and developed symptoms five years earlier than those without the gene mutation.
Auriel Willette, PhD
However, young-to-middle-aged adults with the mutation had a 45% increased risk of developing Parkinson’s disease. Researchers said that the presence of the mutated gene in older adults had minimal effect.
The Potential for Personalized Medicine
It is widely known that rigidity and loss of muscle function associated with Parkinson’s disease are linked to a depletion of dopamine in the substantia nigra. Taking a holistic approach to their study, Dr. Willette and Mr. Webb sought to better understand how the GCH1 gene affects the course of Parkinson’s disease and certain outcomes such as motor skills and anxiety.
The study is the first to look at these biological markers, as well as the first to examine how the gene’s impact on dopamine production specifically affects Caucasian populations. Previous studies have focused primarily on Chinese and Taiwanese populations, said Dr. Willette. The findings have the potential to help personalize medical care for people with a family history of Parkinson’s disease, he said, in a way similar to testing for the BRCA gene in women at risk for breast cancer.
“We want to have a more comprehensive understanding of what these genes related to Parkinson’s disease are doing at different points in someone’s lifetime,” Dr. Willette said. “Then, with genetic testing we can determine the risk for illness based on someone’s age, gender, weight, and other intervening factors.”
The Impact of Age
Data for the study were collected through the Parkinson’s Progression Markers Initiative, a public–private partnership sponsored by the Michael J. Fox Foundation for Parkinson’s Research. The initiative evaluates people with the disease to develop new and better treatments. The Iowa State study included 289 treatment-naïve people recently diagnosed with Parkinson’s disease and 233 healthy controls.
The researchers analyzed anxiety and motor function using the Unified Parkinson’s Disease Rating Scale (UPDRS). They found that those with polymorphisms at rs11158026 coding for the GCH1 enzyme, regardless of age, were more anxious and struggled more with daily activities. The defective gene was not as strong of a predictor of developing Parkinson’s disease in people older than 50, however.
“As we age, we make progressively less dopamine, and this effect strongly outweighs the genetic influences from the ‘bad version’ of this gene,” said Mr. Webb. “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.”
The researchers noted that it is also important to pay attention to blood cholesterol levels. Cholesterol is directly related to the ability to produce dopamine. High low-density lipoprotein (LDL) is an established risk factor for Parkinson’s disease, Dr. Willette said. Their study shows that carriers of the mutated GCH1 gene had higher cholesterol than noncarriers, regardless of age.
Suggested Reading
Webb J, Willette AA. Aging modifies the effect of GCH1 RS11158026 on DAT uptake and Parkinson’s disease clinical severity. Neurobiol Aging. 2017;50:39-46.