Caffeine, creatine, GRIN2A and Parkinson's disease progression.
Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address: dsimon1@bidmc.harvard.edu.
David K
DK
Simon
Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Cai.Wu@uth.tmc.edu.
Cai
C
Wu
Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Barbara.C.Tilley@uth.tmc.edu.
Barbara C
BC
Tilley
Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany. Electronic address: katja.lohmann@neuro.uni-luebeck.de.
Katja
K
Lohmann
Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany. Electronic address: christine.klein@neuro.uni-luebeck.de.
Christine
C
Klein
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Center for Genomic Medicine, HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA. Electronic address: haydehpayami@uabmc.edu.
Haydeh
H
Payami
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: AWILLS@mgh.harvard.edu.
Anne-Marie
AM
Wills
Department of Neurology, University of California, San Francisco, USA. Electronic address: Michael.Aminoff@ucsf.edu.
Michael J
MJ
Aminoff
University of Colorado, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy and Neurology, Aurora, CO, USA. Electronic address: Jacci.Bainbridge@ucdenver.edu.
Jacquelyn
J
Bainbridge
University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: richard.dewey@utsouthwestern.edu.
Richard
R
Dewey
Department of Neurology, University of South Florida, Tampa, FL, USA. Electronic address: rhauser@health.usf.edu.
Robert A
RA
Hauser
Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany. Electronic address: susen.schaake@neuro.uni-luebeck.de.
Susen
S
Schaake
Department of Pathology, Anatomy and Cell Biology, Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Jay.Schneider@jefferson.edu.
Jay S
JS
Schneider
Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: saloni.sharma@chet.rochester.edu.
Saloni
S
Sharma
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address: csinger@med.miami.edu.
Carlos
C
Singer
Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: Caroline.Tanner@ucsf.edu.
Caroline M
CM
Tanner
The Parkinson's and Movement Disorder Institute, Fountain Valley, CA, USA. Electronic address: dtruong@pmdi.org.
Daniel
D
Truong
Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Peng.Wei@uth.tmc.edu.
Peng
P
Wei
University of Colorado, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy and Neurology, Aurora, CO, USA; Singapore General Hospital, Singapore 169608, Singapore. Electronic address: pei.wong@ucdenver.edu.
Pei Shieen
PS
Wong
Department of Biostatistics, University of Texas Health Science Center School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: Tianzhong.Yang@uth.tmc.edu.
Tianzhong
T
Yang
D000368:Aged; D002110:Caffeine / Q000378:metabolism / Q000627:therapeutic use*; D003401:Creatine / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
D002110:Caffeine; D003401:Creatine; D016194:Receptors, N-Methyl-D-Aspartate
Caffeine; Coffee; Creatine; GRIN2A; Parkinson's disease; Progression