Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics

Pharmacogenomics J. 2006 Jan-Feb;6(1):34-41. doi: 10.1038/sj.tpj.6500343.

Abstract

Upregulation of glutamatergic neurotransmission resulting from chronic ethanol intoxication may cause a hyperexcitable state during alcohol withdrawal, which may lead to seizures and delirium tremens. The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens, and a functional polymorphism (Ser310Ala) of the GRIK3 gene coding for the glutamatergic kainate receptor subunit GlurR7 in a sample of well-characterized alcoholics compared to controls. In total, 233 patients meeting DSM-IV alcohol dependence criteria and 309 controls, all of German descent, were investigated. GRIK3 functional polymorphism was determined using PCR (polymerase chain reaction) of lymphocyte DNA. History of alcohol withdrawal-induced delirium tremens and seizures were obtained using the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). Data were cross-checked with in-patients' clinical files. While a significant relationship between history of delirium tremens and the Ser310 allele was detected, no significant results were obtained for alcohol withdrawal-related seizures. Although this result is suggestive for a significant role of this polymorphism in the pathogenesis of delirium tremens in alcohol-dependent individuals, further investigation and confirmation are warranted.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alcohol Withdrawal Delirium / etiology
  • Alcohol Withdrawal Delirium / genetics*
  • Alcohol Withdrawal Seizures / etiology
  • Alcohol Withdrawal Seizures / genetics
  • Alcoholism / complications
  • Alcoholism / genetics*
  • DNA / analysis
  • Female
  • Genotype
  • GluK3 Kainate Receptor
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Kainic Acid / genetics*

Substances

  • Receptors, Kainic Acid
  • DNA