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Brain Samples Reveal Sex-Specific Epigenetic Changes in Mid-Stage Parkinson Disease
The epigenetic changes associated with Parkinson disease differ in men and women, according to study findings published in NPJ Parkinson’s Disease.
“In this genome-wide analysis of DNA methylation in an enriched neuronal population from Parkinson’s disease postmortem parietal cortex, we report sex-specific Parkinson’s disease-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance,” wrote corresponding author Alison I. Bernstein, PhD, and coauthors from the department of translational neuroscience, Michigan State University College of Human Medicine in Grand Rapids.
The study included brain tissue samples from the parietal cortexes of 100 deceased people, 50 of whom had mid-stage Parkinson disease. Analysis revealed more than 200 genes with different epigenetic marks in the brains of people with Parkinson disease and people without the condition. The affected genes, however, diverged in men and women.
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“You could illustrate the male-female divide with two circles depicting genes with different epigenetic markings in Parkinson’s disease, one for men and one for women, and the overlap between the circles would only contain five genes,” said Dr Bernstein, assistant professor of pharmacology and toxicology. “And we’ve found this every time we’ve looked at males and females separately, regardless of whether we’ve been looking at humans or mice or toxicology models. What we call Parkinson’s disease, singular, is probably Parkinson’s diseases, plural.”
Researchers hope the findings will lead toward the identification of genes and pathways that change early in the course of Parkinson’s disease, which could serve as potential targets for treatments to slow or perhaps prevent disease progression.
“Some of the genes we found had already been implicated in other studies, but many of them were brand new,” said Dr Bernstein, who also serves as an assistant professor of pharmacology and toxicology at Rutgers University-New Brunswick, Piscataway, NJ, “so this study opens up many avenues for further investigation of how these other genes are connected to Parkinson’s.”
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