Parkinson’s genetics

Approximately 15% of people with Parkinson have a family history of the condition and about 10-20% of Parkinson’s cases are associated with genetic variations that infer a higher risk of developing the condition. In people with ‘early-onset’ Parkinson’s (diagnosed before the age of 50), genetic variations are associated with more cases than later onset Parkinson’s, where the frequency of genetic variations is less common.

It is important to note, however, that having a genetic variation does not immediately mean that someone is going to develop Parkinson’s. There are many people who have these mutations in their DNA and never show any signs of the condition; researchers are trying to establish the factors that influence this situation.

Some of the better studied genetic risk factors associated with increased risk of Parkinson’s, include:

GBA

Small genetic variations in a region of DNA called the GBA gene are linked with an increased risk of developing Parkinson’s; the GBA gene provides instructions for making an enzyme called GCase, or glucocerebrosidase, which enables cells to clear waste compounds effectively. In individuals with Parkinson’s who carry a fault in their GBA gene, GCase function is lowered resulting in faulty waste clearing from cells; so researchers have been looking to identify medicines that can enhance the level of GCase activity in the body thereby potentially slowing the progression of Parkinson’s. One example of this is the cough medication called ambroxol, which Cure Parkinson’s is currently repurposing for Parkinson’s.

LRRK2

Genetic variations within the LRRK2 gene are also recognised as being some of the most common with regards to increasing a person’s risk of developing Parkinson’s – LRRK2 variants are present in approximately 1-2% of all cases of Parkinson’s.

PINK1

The PINK1 gene runs in families and is associated with early-onset Parkinson’s; PINK1 provides instructions for cells to make a protein called PTEN induced putative kinase which is present in the mitochondria of cells throughout the body. Mitochondria are the ‘battery packs’ in cells used to produce the energy they need to function.

Scientists believe PTEN induced putative kinase protects mitochondria when cells are under stress, and mutations in the PINK1 gene could then mean that mitchondria are not protected as well. Mutations of the PINK1 gene are rare, but scientists believe they may contribute to early-onset Parkinson’s disease.

PRKN

The PRKN gene is responsible for making a protein called parkin and many PRKN gene variants have been linked to Parkinson’s. PRKN is the most common variant associated with early-onset Parkinson’s; those people with Parkinson’s who have this gene may experience early symptoms such as slowness of movement and freezing.

Research has shown that PRKN gene variants cause a dysfunctional version of the parkin protein which may affect the production of dopamine. In people with Parkinson’s, the brain gradually stops making dopamine leading to the characteristic problems of Parkinson’s, associated with movement and balance. Variants in the PRKN gene may also affect mitochondria – the energy sources of cells, and research suggests that this dysfunction could play a role in causing Parkinson’s. Researchers are studying treatments that could enhance parkin protein activity.

Importantly, understanding what the connections are between Parkinson’s and the underlying genetics can help us to further comprehend how the condition develops and progresses, and how we can treat it and ultimately cure it.

There are now a number of clinical trials testing drugs in people with Parkinson’s who also have certain gene mutations.