Genetic Variations Related to Gastrointestinal System Linked to Parkinson’s

- Jun 17 2014

A new study bolsters the theory that Parkinson’s disease (PD) may begin in the digestive system.  In research published in the May 17 online edition of Movement Disorders, scientists report that variations in the genes for certain intestinal proteins responsible for keeping the gut healthy may be associated with an increased risk of PD.

The human intestines are lined with trillions of microorganisms, some helpful and others harmful. Several lines of evidence point to a role for the digestive tract early in PD. For example, clumps of alpha-synuclein – the hallmark of PD in the brain – have been found in nerve cells of the colon in people who later developed PD. In addition, constipation is a common early symptom of PD, as are inflammation of the gut and an overgrowth of certain bacteria in the small intestine. 

Researchers led by Samuel M. Goldman, M.D., M.P.H., at the San Francisco Veterans Affairs Medical Center, wanted to understand whether genetics can explain why some people develop PD and others may not. Following up on the gut-PD link, they asked whether variations in the genes encoding key proteins in the intestines may be correlated with increased or decreased risk for PD. These gut proteins are called peptidoglycans and help the body’s immune system recognize and respond to bacteria.  But the components of these proteins can vary slightly from person to person.  

To test whether variations in the genes for the peptidoglycans proteins were associated with PD risk, the researchers analyzed DNA in blood samples collected from 518 people with PD and 543 healthy individuals. Participants were drawn from two earlier studies.

Results

• Common variants in three of four genes encoding peptidoglycan proteins were associated with an altered risk of PD – both decreased and increased risk.
• The results were similar in two distinct populations of people with PD.

What Does It Mean?

This study is the first to link genetic variations in bacteria-responsive gut proteins called peptidoglycans to Parkinson’s disease. In light of other associations between the gut and PD, the authors suggest that peptidoglycan proteins may play a role in causing the disease by influencing a person’s immune response to bacteria in the gut. Because this epidemiological study did not actually demonstrate that these genetic variations actually precipitated PD, further research is needed to discover the mechanisms by which these proteins are linked to PD. Nevertheless, this study helps define a new direction for scientists to pursue an understanding and potential treatment to Parkinson’s disease.

Reference: Goldman SM, Kamel F, Ross GW, Jewell SA, Marras C, Hoppin JA, Umbach DM, Bhudhikanok GS, Meng C, Korell M, Comyns K, Hauser RA, Jankovic J, Factor SA, Bressman S, Lyons KE, Sandler DP, Langston JW, Tanner CM (2014) Peptidoglycan recognition protein genes and risk of Parkinson's disease. Mov Disord. Ahead of Print DOI:10.1002/mds.25895http://dx.doi.org/10.1002/mds.25895