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Protective Effect of Coffee in Parkinsonís has a Genetic Basis

Scientists have long observed that that those who drink caffeinated coffee are at a lower risk of developing Parkinson’s disease (PD).  But all people do not benefit equally; there are people who consume high doses of caffeine who go on to develop Parkinson's. Now researchers have discovered that the gene known as GRIN2A influences coffee’s protective effect. The results were reported in the August 11, 2011 issue of PLoS Genetics.

To search for genes that either magnify or reduce coffee’s protective effect in Parkinson’s, researchers led by Haydeh Payami, Ph.D., at the New York State Department of Health Wadsworth Center, turned to a technique called a genome-wide association study (GWAS).  This method scans specific sections of DNA of thousands of people for small variations or differences called single-nucleotide polymorphisms (SNPs).  Certain SNPs found only in people with a particular disease are then studied further to see if they play a role in that disease.

Dr. Payami and her colleagues took the GWAS technique a significant step further by evaluating how the SNPs they found interacted with coffee.  They analyzed the genomes of 1,458 people with Parkinson’s and 931 people without Parkinson’s, combined with data on lifetime consumption of caffeinated coffee. To examine coffee’s effect in more detail, the scientists divided the coffee drinkers into two groups, heavy and light coffee drinkers, meaning those who drank more or less (including non-drinkers) than the median amount among study participants.

Results

  • The researchers found a cluster of variations, or SNPs, in the gene GRIN2A, which regulates brain signals that control movement and behavior.
  • On average, heavy coffee drinkers were found to have a 27 percent lower risk of Parkinson’s.
  • The risk of developing Parkinson’s was even less for heavy coffee drinkers that carried a variant of GRIN2A; compared to light coffee drinkers, Parkinson’s risk was 59 percent lower for heavy coffee drinkers with one variant of GRIN2A, but only 18 percent lower among those with a different yet more common variant.

What Does It Mean?

At its simplest, the new study suggests that whether drinking coffee lowers a person’s risk of Parkinson’s depends on which variant of the GRIN2A gene they carry.  But the research also has broader implications for testing new PD therapies, according to the study authors.  Two classes of potential Parkinson’s drugs, one that works on the brain in a similar way to the way caffeine found in coffee does (adenosine antagonists) and another that interacts with GRIN2A (glutamate antagonists), have been found safe in clinical trials for Parkinson’s. Adenosine antagonists are being studied now in clinical trials as potential treatment in different stages of Parkinson’s.  The authors suggest that such drugs may be effective in a subset of clinical trial participants who carry the appropriate variation of GRIN2A.  In the future, genetic testing for GRIN2A or other genetic variations might be used in clinical trials to determine which participants are more likely to respond to a therapy being tested. This would potentially be a first step towards a personalized medicine approach in the treatment of Parkinson’s.

Reference: Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu S-A, Scott WK, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee. PLoS Genetics. 2011 Aug.;7(8):e1002237.

Source Date: Dec 08 2011