Mimetism of genetic mutations by low-weight compounds

Analysis of gene mutations in populations in endemic areas where a disease is broadly distributed might help better understanding if the genetic mutations provide advantages or well-being with respect to the disease, or if contrary, the genetic mutations favors morbidity and accelerate deaths to the populations affected by the disease. The frequency, as wells as the number of mutation points, might bring complementary information on the "metabolic compensation" brought by the mutation with respect to the disease.

As examples: methemoglobinopathies, genetic deficiencies in glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase genes are known to protect the populations at risk for malaria from severe episodes, like coma and cerebral malaria. This is due to the fact that these mutations increase the oxidative stress in erythrocytes, rendering the milieu hostile for malaria parasites. These clinical observations were supported by evidence of a shorter half-life of red blood cells in these mutated populations by the immune system. Fast removal of erythrocytes prevents the completion of the parasitic cycle in erythrocytes to proceed.

The strong correlations between these genetic mutations and the disease can also be correlated with the nutritional habits of the populations. Analysis of the nutritional habits in the geographical area where a disease is broadly distributed might classify correlation parameters as favorable or adverse with respect to the onset, or the progress, or the extent of the disease.

As examples: the favism is the haemolytic response due to the consumption of broad beans by individuals with G6PD deficiency. At the cellular level, the beans release natural compounds which deplete the red blood cells in glutathione which the guardian for reducing power in the cells by preventing damage from oxidizing free radicals. In G6PD-deficient populations, who formely have red blood cells with defected reducing milieu, the natural redox-active compounds from beans increase the oxidative stress to a tremendous and toxic level responsible for hemolytic anemia.