The MTHFR C677T mutation is known to results in a deficiency of the enzymes activity and an increased risk for several disease states such as miscarriage, birth defects and heart disease. While these effects are highly undesirable, the mutation is prevalent in many populations, with the Mediterranean region having one of the highest frequencies worldwide. It is also in this region that rates of malaria are consistently high compared in comparison to other regions. Therefore, Meadows et al (2014) examined mice for a link between a mutation in the MTHFR C677T gene and the prevalence of malaria, hypothesizing the high rates of C677T polymorphisms in the region could be occurring in order to play a role in protecting against malarial infection.
Mice with the MTHFR mutation along with mice altered to over-express the C677C normal gene were infected with malaria to study their reaction and survivability. Mice with the mutation survived longer, with the mice over-expressing dying earlier after injection compared to mice with the wild-type (normal C677C presentation). The mice with the MTHFR mutation were found to have an increased level of NK cells in the spleen, with the mice over-expressing the gene showing decreased numbers. Compared to mice with a normal C677C presentation, those with the mutation were found to have increased levels of proteins involved in the immune response.
Overall, the authors suggested a mild mutation in the MTHFR C677T gene protects against malarial infection, which could have led to the high prevalence of this mutation occurring in human populations.