title: Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population.
abstract: A complex interplay between genetic and environmental factors is thought to be involved in the etiology of Parkinson's disease (PD). A recent genome-wide association and interaction study (GWAIS) identified GRIN2A, which encodes an NMDA-glutamate-receptor subunit involved in brain's excitatory neurotransmission, as a PD genetic modifier in inverse association with caffeine intake. Here in, we attempted to replicate the reported association of a single nucleotide polymorphism, GRIN2A_rs4998386, and its interaction with caffeine intake with PD in patient-control study in an ethnically homogenous population in southeastern Sweden, as consistent and independent genetic association studies are the gold standard for the validation of genome-wide association studies. All the subjects (193 sporadic PD patients and 377 controls) were genotyped, and the caffeine intake data was obtained by questionnaire. We observed an association between rs4998386 and PD with odds ratio (OR) of 0.61, 95% confidence intervals (CI) of 0.39-0.96, p = 0.03, under a model excluding rare TT allele. There was also a strong significance in joint effects of gene and caffeine on PD risk (TC heavy caffeine vs. CC light caffeine: OR = 0.38, 95%CI = [0.20-0.70], p = 0.002) and gene-caffeine interaction (OR = 0.998, 95%CI = [0.991-0.999], p<0.001). Overall, our results are in support of the findings of the GWAIS and provided additional evidence indicating PD protective effects of coffee drinking/caffeine intake as well as the interaction with glutamate receptor genotypes.
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Naomi
authors.initials: N
authors.lastname: Yamada-Fowler
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002110:Caffeine / Q000494:pharmacology*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012307:Risk Factors; D013548:Sweden
chemical_list: D002110:Caffeine; D016194:Receptors, N-Methyl-D-Aspartate