Specific genes and changes in their expression may impact on a person’s risk of developing Parkinson’s disease (PD), researchers from Boston University School of Medicine (BUSM) reported in the journal PLOS ONE.

The researchers say they have carried out the first ever genome-wide evaluation of genetic variants linked to Parkinson’s disease.

Jeanne Latourelle, DSc, and Richard H. Myers, PhD, explained that a recent study published by the PDGC (PD Genome Wide Association Study Consortium) had shown that people with genetic variants in or close to the genes HLA, MAPT, SNCA, RIT2, and GAK/DGKQ had a higher-than-average risk of developing Parkinson’s disease. However, in that study, the mechanism behind the higher risk had not been determined.

Boston University School of Medicine reported in PLOS ONE in July 2012 that the FOXO1 gene plays an important part in the pathological mechanisms of Parkinson’s disease. That study is said to have used the largest number of brain samples used in a wide-genome expression study of PD.

Latourelle suggested that perhaps a genetic variant might change how a gene is expressed in the brain, resulting in a higher risk of developing Parkinson’s.

The scientists say that their findings may pave the way for treatments to correct the genetic variants and thus possibly reverse the effects of Parkinson’s disease.

Latourelle and colleagues set out to determine what the relationship might be between PD-associated genetic variants and levels of gene expressions detected in the frontal cortex of 26 people who had been diagnosed with Parkinson’s disease, with 24 samples from the brains of healthy individuals.

They determined gene expression by using a microarray that screened what the effects of genetic variants were on the expression of genes located very near the variant – called cis-effects – and genes that were far from the variant, such as genes on a totally different chromosome, called trans-effect. To recap – cis-effects are those on very nearby genes, while trans-effect are those on distant genes.

When they analyzed the cis-effects, it was observed that many genetic variants in the MAPT region showed a significant association with the expression of multiple nearby genes, including gene LOC644246, the duplicated genes LRRC37A and LRRC37A2, and the gene DCAKD.

They also observed significant cis-effects between variants in the HLA region on chromosome 6 and HLA-DQA1 and HLA-DQA1, two genes that were very near.

Myers said:

“The identification of the specific altered genes in PD opens opportunities to further study them in model organisms or cell lines with the goal of identifying drugs which may rectify the defects as treatment for PD.”

In December 2011, scientists from Neuroscience Research Australia and the University of New South Wales, Sydney, Australia, found that genetic factors can predict the progression of Parkinson’s disease.

Specialist doctors have known for years that certain risk factors, including genetic ones, are associated with a higher risk of developing Parkinson’s disease. Below are the most commonly described risk factors:

  • Age – older people have a much higher risk of developing Parkinson’s disease, compared to individuals who are young. Some younger people have developed PD, but this is very rare.
  • Genetics – if you have a close relative who has/had Parkinson’s disease, your risk of developing it yourself is slightly higher-than-average. A close relative means a brother, sister, mother or father. This study looked at the genetic link very closely.
  • Sex – men have a slightly greater risk of developing PD than women.
  • Exposure to some toxins – people who have been exposed to some types of pesticides, herbicides, or carbon monoxide are more likely to develop PD than others.
  • Some prescription drugs – such as those used for the treatment of psychosis and severe paranoia can cause Parkinsonism (conditions with Parkinson’s-like symptoms)

Written by Christian Nordqvist