Parkinson's Disease Genetic Link That Implicates the Immune System

Hunt throughout the human genome for variants associated with common, late-onset Parkinson's disease has revealed a new genetic link that implicates the immune system.

The long-term study involved a global consortium, including Johns Hopkins researchers from the Center for Inherited Disease Research (CIDR) who performed genome-wide association studies on more than 4,000 DNA samples — half from unrelated patients with Parkinson's and half from healthy "controls." The team confirmed that a gene in the human leukocyte antigen (HLA) region was strongly linked with Parkinson's disease; this region contains a large number of genes related to immune system function.

The new data bolsters previous studies that hinted about a role for infections, inflammation and autoimmunity in Parkinson's disease. This genetic finding demonstrates that inflammation isn't simply a result of having Parkinson's disease, but somehow is involved as a player in its origin.

"This is an exciting finding from a genome-wide association study (GWAS) which is completely hypothesis-independent and bias-free, based solely on looking at the whole genome and finding out what genes might be related to Parkinson's," says Kimberly Doheny.

It was long believed that common, late-onset Parkinson's had no genetic components — that environmental factors were the exclusive cause. Since genes were first implicated almost two decades ago, Parkinson's has proven itself a "tough nut to crack," Doheny says, adding that a handful of GWAS done prior to this one revealed nothing new other than to confirm genes that previously had been found to confer risk.

Setting this GWAS study apart, Doheny says, was the investigators' meticulous choosing of patients and care of the DNA samples tested. The study's principal investigator Haydeh Payami describes CIDR's contribution as "huge."

It took 18 years to build the study, according to Payami, at whose insistence the collection of DNA and clinical information was standardized using the most rigorous research criteria. Patients from whom samples were taken were tracked for at least a dozen years after their initial diagnoses to assure that they indeed had Parkinson's, Payami adds, explaining that about 20 percent of Parkinson's disease patients' diagnoses are actually misdiagnoses.

A neurodegenerative disease affecting between 1 and 2 percent of people over the age of 65, Parkinson's disease can be difficult to diagnose as no definitive test exists. Its symptoms, which include tremors, sluggish movement, muscle stiffness and difficulty with balance, can be caused by many other things, including other neurological disorders, toxins and even medications.

The GWAS itself took about four months, Doheny says, and cost about $400 per sample tested; whole-genome sequencing costs about $10,000 per sample.

Since 1996, CIDR has provided high-quality genotyping services and statistical genetics consultation to gene hunters: researchers who are working to discover genes that contribute to common diseases by ferreting out variants in the genome. Its role in the Parkinson's study was to assure that the genotyping dataset was of high quality, that data cleaning was done appropriately and that association analysis was stringent.

"We now have another window into what may be going on in Parkinson's," Payami says. "This finding anchors the idea of immune system involvem

What Is the Best Diet for Parkinson's Disease?

The best diet for Parkinson's disease is similar to the best diet for most people, which includes eating lots of fresh fruit and vegetables, preferring fish and dairy protein to meat, and eating whole grain foods. No specific diet has consistently been recommended for those with Parkinson's disease. That said, people with Parkinson's disease may benefit from some dietary changes.

Parkinson's disease is caused by increasing damage to the brains cells that produce dopamine. Dopamine is a chemical messenger that is necessary for making smooth, controlled movements, among other things. The decrease in dopamine results the most familiar symptoms of Parkinson's disease, including tremors and a shuffling gait. The dopamine deficit at the root of Parkinson's disease cannot be treated by diet alone. Eating healthy foods, though, along with beneficial fats from nuts and legumes, will supply adequate nutrition.

The risk of developing Parkinson's disease has been linked to insufficient vitamin D intake. Raising vitamin D intake in a diet for Parkinson's disease probably won't have a therapeutic effect, but it may make bones healthier. People with Parkinson's disease seem to be at more risk for osteoporosis, a condition in which the bones become weaker and more prone to breaking. Vitamin D can be obtained in supplements containing 400-1,000 international units (IUs) of this vitamin. Good food sources of Vitamin D include milk and fatty fish like salmon and sardines.

People with Parkinson's are often prescribed l-dopa, a prescription drug that can raise dopamine levels in the brain. One strategy in a diet for Parkinson's disease includes eating very little protein at breakfast and lunch, and getting most dietary protein at dinner. This strategy seems to increase the effectiveness of the l-dopa drug. As with other broad dietary changes, this should be done in consultation with a qualified dietitian to ensure the diet provides enough protein as well as overall nutrition.

Those with Parkinson's disease can become constipated more easily than the general population. Drinking plenty of water and eating more fiber are good strategies for a diet for Parkinson's disease, especially one aimed at relieving constipation. Fiber intake can be raised by eating more fruits, vegetables, and whole grains, or by taking a fiber supplement.