Association was detected between HLA region and late-onset sporadic disease.

A team of researchers report finding evidence that Parkinson disease may have an infectious or autoimmune origin. The investigators detected a new association with the HLA (human leukocyte antigen) region, which contains a large number of genes related to immune system function in humans.

Results are published in Nature Genetics, and the paper is titled “Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease.” The study was conducted by the NeuroGenetics Research Consortium, an international team of scientists led by Haydeh Payamiof the New York State Department of Health Wadsworth Center.

HLA genes are essential for recognizing foreign invaders from the body’s own tissues, but the system doesn’t always work perfectly. HLA genes are highly variable from individual to individual. Certain variants of the genes are associated with increased risk of or protection against infectious disease, while other variants can induce autoimmune disorders.

A genome-wide association study was performed on 2,000 Parkinson disease patients and 1,986 healthy volunteers from clinics in Oregon, Washington, New York, and Georgia. The scientists looked at clinical, genetic, and environmental factors that might contribute to the development and progression of the disease and its complications. Some research subjects were reportedly tracked for nearly two decades.

The team confirmed associations with the genes SNCA and MAPT, replicated an association with the gene GAK, and detected a new association with the HLA region. The HLA link was replicated in two datasets and was uniform across all genetic and environmental risk strata, the team reports. Additionally, it was strong in sporadic and late-onset disease.

“Our results also pointed to several other genes that might play a role in developing Parkinson’s disease, and these findings need to be confirmed, so we have a lot of work ahead of us,” notes Cyrus Zabetian, M.D., associate professor of neurology at the University of Washington and VA Puget Sound Health Care System. He and others in the consortium will now mine for gene-environment interactions, with a goal of finding environmental triggers and protectors to develop personalized therapeutics for treatment and prevention of Parkinson disease.

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