Polymorphism

See Also

• Glucose-6-phosphate dehydrogenase deficiency

Description

Inside the boundary membrane of the red cell is a solution containing a great variety of proteins, including haemoglobin and numerous enzymes many of which have several allelic variants. The variants often show quantitative differences in efficiency. One enzyme with such variants is glucose 6-phosphate dehydrogenase. This protein is needed for maintaining the integrity of the red cell.

Discussion

In the Mediterranean region of the world, we find that many people there are very sensitive to fava beans. Consumption of these beans results in potentially life-threatening damage to their red blood cells, spontaneous bleeding and anemia. Fava beans contain a specific substance that can poison the activity of a very important enzyme called glucose-6-phosphate dehydrogenase (G6PD), which is found in red blood cells and is very important for the maintenance of their structure and function. People of Mediterranean heritage who inherit a genetic deficiency of the G6PD enzyme are much more susceptible to this toxic substance found in fava beans.

Interestingly, geneticists have found the G6PD deficiency characteristic is the most common human genetic variation that has yet been identified. It is found in many forms and degrees. Some individuals whose genes express much more G6PD deficiency than others may be much more sensitive to fava beans. Not all individuals will react in the same way. Fava bean sensitivity is another example of the way a specific food and substances within it influence the function of the gene products of individuals who carry certain inheritance factors. Fava beans, which are considered a nutritious food for many individuals, are consumed in large quantities in the Middle East. For those who carry the G6PD deficiency inheritance factor, however, eating fava beans can be dangerous.(1)

Genomics

Gene type: protein coding Gene name: G6PD Gene description: glucose-6-phosphate dehydrogenase Organism: Homo sapiens Gene aliases: G6PD1 Chromosome: X; Location: Xq28

Summary

This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia.

Literature review

• Nearly 150 different G6PD variants have been described. The recent determination of its 3-dimensional structure explains the mechanisms of G6PD deficiency in terms of structure-function relationship. PubMed
• G6PD is a candidate gene for diabetes. PubMed
• Significant difference in distribution of G6PD activities as grouped by an increment of 100 U/10(12) red blood cells (RBCs) was observed between diabetic patients and healthy subjects. PubMed

Discussion

The gene concerned is carried on the X chromosome, so that males have only one such gene but females have two. In males with a deficient gene or in females with two such genes there is a tendency for the red cell to break down if the individual consumes certain drugs, or the common broad bean (Vicia faba).(2)

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References