Since we have been discussing lack of immunity of raw fooders to malaria, we might ask ourselves if there are some genetic factors which protect against it. Here is the beginning of an answer: People who lack the ability to produce the enzyme G6PD are resistant to malaria. On the other hand, lacking that enzyme causes some health problems, like susceptibility to favism (for people who eat fava beans). ---------------------------------------------------------------------- Blood Rev 1996 Mar;10(1):45-52, G6PD: population genetics and clinical manifestations, Beutler E The glucose-6-phosphate dehydrogenase (G6PD) gene is X-linked. There are numerous mutations that cause a deficiency of this enzyme in erythrocytes. G6PD deficiency can produce anemia, both when drugs are administered and under the stress induced by infection. Functionally severe variants cause hereditary non-spherocytic hemolytic anemia, i.e. anemia even in the absence of stress. Neonatal jaundice occurs in G6PD deficiency, but it is likely that it is largely due to impairment of liver function, rather than to hemolysis. It has been suggested that there are clinical manifestations of G6PD deficiency that are related to other tissues, but the existence of these is not well documented. Some mutations that produce G6PD deficiency in red cells exist at polymorphic frequencies. Individuals with such mutations seem to have enjoyed a selective advantage because of resistance to falciparum malaria. Different mutations, each characteristic of certain populations, are found, and have been characterized at the deoxyribonucleic acid (DNA) level. G6PD A-(202A376G) is the most common African mutation. G6PD Mediterranean(563T) is found in Southern Europe, the Middle East and in the Indian subcontinent. Several other mutations are common in Asia. Genetic variability of G6PD has played an important role in the understanding of a variety of developmental processes. ------------------------------------------------------------------ Southeast Asian J Trop Med Public Health 1991 Jun;22(2):176-182, G6PD deficiency and fava bean consumption do not produce hemolysis in Thailand, Kitayaporn D, Charoenlarp P, Pattaraarechachai J, Pholpoti T Favism, a hemolytic condition associated with fava bean consumption among the glucose-6-phosphate dehydrogenase (G6PD) deficient persons, is well described in the Middle East and Mediterranean areas. However, it is not well documented among the Thais or other Southeast Asians. It is possible that it does exist but that hemolysis which develops is of very minor degree and thus escapes clinical detection. This cross-sectional study hypothesizes that if the fava bean and G6PD deficiency interact in the Thai population, they should cause a significant difference in hematocrit level. The study was carried out in a community hospital in a malaria endemic area. We found that there was a trivial difference of the hematocrit (approximately 1%) which was too small to warrant any clinical significance after controlling for the extraneous effects of age, sex, use of malaria chemoprophylaxis, falciparum infection, use of analgesics/antipyretics and admission status of the patients (p = 0.668). This may be due to the presence of different G6PD mutants to those found elsewhere or due to different consumption patterns of fava beans among the Thais compared to people in other areas with high prevalence of G6PD deficiency. ------------------------------------------------------------------------- Bioessays 1996 Aug;18(8):631-637, A new lease of life for an old enzyme, Martini G, Ursini MV We review here some recent data about glucose-6-phosphate dehydrogenase (G6PD), the first and key regulatory enzyme of the pentose phosphate pathway. New evidence has been presented to suggest that malaria is a selective agent for G6PD deficiency, which is the most common enzymopathy in man, and that G6PD deficiency, generally considered to be a mild and benign condition, is significantly disadvantageous in certain environmental conditions. At the molecular level, the enzyme structure has recently been elucidated and mechanisms regulating G6PD gene expression have been determined. A G6PD knock-out mutation introduced in mouse cells makes them exquisitely sensitive to oxidative stress, indicating that this ubiquitous metabolic enzyme has a major role in the defence against oxidative stress, even in eukaryotic nucleated cells, which have several alternative routes for providing the same protection. Because of the high prevalence of G6PD deficiency in many populations, it is expected that these findings will prompt further studies to ascertain the putative role of G6PD deficiency in conditions such as carcinogenesis and ageing.