Glutathione reductase deficiency in Saudi Arabia

Abstract

Glutathione reductase [GR]is a ubiquitous enzyme required for the conversion of oxidized glutathione [GSSG] to reduced glutathione [GSH] concomitantly oxidizing reduced nicotinamide adenine dinucleotide phosphate [NADPH]in a reaction essential for the stability and integrity of red cells. Mutations in the GR gene and nutritional deficiency of riboflavin, a co-factor required for the normal functioning of GR, can cause GR deficiency. We conducted a study on 1691 Saudi individuals to determine the overall frequency of GR deficiency and to identify whether the deficiency results from genetic or acquired causes or both. The activity of GR was measured in freshly prepared red cell haemolysate in the presence and absence of flavin adenine dinucleotide [FAD]and the activity coefficient [AC] was determined. Samples with low GR activity [>2.0 IU/g haemoglobin] both in the presence and absence of FAD and an AC between 0.9 and 1.2 were considered GR-deficient. Samples with AC >/= 1.3 were considered riboflavin-deficient. The overall frequency of partial GR deficiency was 24.5% and 20.3% in males and females respectively. In addition, 17.8% of males and 22.4% of females suffered from GR deficiency due to riboflavin deficiency. This could be easily corrected by dietary supplementation with riboflavin. No cases of severe GR deficiency were identified

Monogenic Disorders of ROS Production and the Primary Anti-Oxidative Defense

“…However, in the few studies available, no other possible genetic causes for the described symptoms were genetically excluded, e.g., by whole exome analysis. That humans can be rather robust toward reduced GSR activity is also exemplified by the high frequency of moderate GSR deficiency due to malnutrition, specifically due to the lack of riboflavin, which is a precursor of the GSR cofactor flavin adenine dinucleotide (FAD) in some populations [141,142].…”