Mutant gene conclusively linked to Parkinson's disease

New research into a rare genetic disorder called Gaucher disease has revealed a genetic predisposition for people with this disease to Parkinson's disease. The study, published last week in the New England Journal of Medicine, was carried out because in the past some clinicians have noticed a link between the two diseases.

Parkinson's disease is a neurological condition that results in tremors and stiffness in movement, affecting one to two per cent of people over 60. It is caused by a combination of genetic and environmental factors, and scientists have previously found many genes linked to it. This research, however, conclusively proves that this particular mutation is one of the most significant risk factors found so far for Parkinson's.

Gaucher disease occurs when a person inherits two copies of a mutation in the GBA gene, coding for an enzyme called glucocerebrosidase. Its function is to break down glucocerebroside, but when this is not disposed of properly it can harm the spleen, liver, lungs, bone marrow and, in some cases, the brain. People with only one defective GBA copy are not affected by Gaucher disease, but are carriers. About one in 100 people in the US carry the gene, but the incidence among particular groups is increased, for example one in 15 Ashkenazi Jews carry the gene.

Dr Ellen Sidransky, senior investigator at the National Human Genome Research Institute's Medical Genetics Branch, led the study in which data was collected from all of the Gaucher disease researchers in the world - 64 researchers at 16 institutions. They studied two common GBA variants in 5,691 people with Parkinson's disease, including 780 Ashkenazi Jews, comparing them to 4,898 disease-free individuals, including 387 Ashkenazi Jews.

They found that 3.2 per cent of the Parkinson's patients had at least one of the common GBA variants, compared with 0.6 per cent of healthy people, which is a five-fold increase. Among the Ashkenazi patients, 15.3 per cent had one of the common GBA variants, compared with 3.4 per cent of healthy Ashkenazi controls. Importantly, they emphasise that not all Gaucher patients develop Parkinson's, indicating that other factors must also be at work.

Five of the research centres also sequenced the entire GBA gene in 1,642 non-Ashkenazi patients with Parkinson's and 609 healthy non-Ashkenazis, and found many other alterations associated with Parkinson's disease. They showed that seven per cent of patients carried a variant, indicating that their risk of developing Parkinson's was ten times normal.

Additionally, the variants also appear to influence early onset of Parkinson's disease; Parkinson's patients with the GBA variants developed the disease on average four years earlier than other Parkinson's patients.

Despite that these results do not directly aid researchers in developing treatments for the diseases, the study has thrown up important information into the risk factors of Parkinson's and how the disease develops and progresses. Sidransky says that 'it gives us new theories and ideas that have all kinds of clinical and therapeutic implications', and also that 'it is a great example of why it is important to study rare genetic disorders. Because sometimes you end up with findings that have implications not only for the rare disorder but also for the common disease'.