Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population

PLoS One. 2014 Jun 10;9(6):e99294. doi: 10.1371/journal.pone.0099294. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Caffeine / pharmacology*
  • Case-Control Studies
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Risk Factors
  • Sweden

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Caffeine
  • N-methyl D-aspartate receptor subtype 2A

Grant support

This study was funded by the Foundation for Parkinson's Research at Linköping University, Sweden (Stiftelsen för Parkinsonforskning, 20110525). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.