An association study of sodium-lithium countertransport activity with glutathione S transferase (GST) T1 and GST M1 null polymorphisms in Greek dyslipidaemic patients and controls

Clin Chem Lab Med. 2008;46(3):306-10. doi: 10.1515/CCLM.2008.065.

Abstract

Background: Previous genomic linkage studies have produced evidence linking sodium-lithium countertransport activity (Na/Li CT) with various chromosomal regions including loci harbouring glutathione S transferase (GST) genes. The aim of this study was to examine the putative association of erythrocyte Na/Li CT activity with GST T1 and M1 gene null polymorphisms.

Methods: Na/Li CT activity was determined in erythrocytes isolated from 85 individuals, using a standard assay procedure employing atomic absorption spectroscopy. Genotyping of the GST T1 and GST M1 null polymorphisms was accomplished with a multiplex PCR method. A general linear model using age, sex, smoking, dyslipidaemia and hypertension as covariates was used to examine the association of Na/Li CT activity with the GST T1 and GST M1 genotypes.

Results: Individuals with the GST T1 null genotype displayed marginally significantly (p=0.049) lower values of Na/Li CT activity compared to those harbouring at least one copy of the GST T1 gene. The significance of this association was eliminated following adjustment for covariates (p=0.150), but survived as a trend when the sample was limited to normotensive and normolipidaemic individuals (p=0.070). No association was detected between the GST M1 null polymorphism and Na/Li CT activity.

Conclusions: The suggestive association of the GST T1 null polymorphism with erythrocyte Na/Li CT activity is in line with previously published data from genetic linkage and biochemical analyses and may be of potential prognostic value as regards the behaviour of the countertransport and the development of related pathologies under conditions of oxidative insult.

MeSH terms

  • Antiporters / metabolism
  • Case-Control Studies
  • Dyslipidemias / complications
  • Dyslipidemias / genetics*
  • Dyslipidemias / metabolism*
  • Erythrocytes / metabolism
  • Female
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / metabolism
  • Greece
  • Humans
  • Hypertension / complications
  • Hypertension / genetics
  • Hypertension / metabolism
  • Ion Transport
  • Lithium / metabolism*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Protein Binding
  • Sodium / metabolism*

Substances

  • Antiporters
  • sodium-lithium countertransporter
  • Lithium
  • Sodium
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1