The concentration of glutathione in human erythrocytes is a heritable trait.
Glutathione (GSH) is a ubiquitous, redox-active, small molecule that is critical to cellular and organism health. In red blood cells (RBCs), the influence of the environment (e.g., diet and lifestyle) on GSH levels has been demonstrated in numerous studies. However, it remains unknown if levels of GSH are determined principally by environmental factors or if there is a genetic component, i.e., heritability. To investigate this we conducted a twin study. Twin studies are performed by comparing the similarity in phenotypes between mono- and dizygotic twin pairs. We determined the heritability of GSH, as well as its oxidation product glutathione disulfide (GSSG), the sum of GSH equivalents (tGSH), and the status of the GSSG/2GSH couple (marker of oxidation status, Ehc) in RBCs. In our study population we found that the estimated heritability for the intracellular concentration of GSH in RBCs was 57 %; for GSSG it was 51 %, tGSH 63 %, and Ehc 70 %. We conclude that a major portion of the phenotype of these traits is controlled genetically. We anticipate that these heritabilities will also be reflected in other cell types. The discovery that genetics plays a major role in the innate levels of redox-active species in RBCs is paradigm shifting and opens new avenues of research in the field of redox biology. Inherited RBC antioxidant levels may be important disease modifiers. By identifying the relative contributions of genes and the environment to antioxidant variation between individuals, new therapeutic strategies can be developed. Understanding the genetic determinants of these inherited traits may allow personalized approaches to relevant therapies.
Interdisciplinary Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USA.
Thomas J
TJ
van 't Erve
Free Radical and Radiation Biology Program, Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
Brett A
BA
Wagner
Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA.
Kelli K
KK
Ryckman
Department of Pathology, Carver College of Medicine, and The University of Iowa, Iowa City, IA 52242, USA.
Thomas J
TJ
Raife
Free Radical and Radiation Biology Program, Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: garry-buettner@uiowa.edu.
Garry R
GR
Buettner
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D005978:Glutathione / Q000032:analysis* / Q000235:genetics*; D019803:Glutathione Disulfide / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019655:Quantitative Trait, Heritable; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055815:Young Adult
D005978:Glutathione; D019803:Glutathione Disulfide
BDD; DZ; Free radicals; GSH; GSSG; Glutathione; Heritability; ICC; MZ; RBC; Red blood cells; Twin study; boron-doped diamond electrode; dizygotic; glutathione; glutathione disulfide; intraclass correlation coefficient; monozygotic; red blood cell; tGSH; total GSH equivalents, i.e., [tGSH]=[GSH]+2[GSSG].