Review: Folate Metabolism, Genes + Polymorphisms

This review article by Nazki et al (2014) examined the evidence currently available on folate, methylation and genetic polymorphisms. It lists the main functional polymorphisms of the MTHFR gene to be C677T and A1298C. In regards to the C677T mutation, the heterozygous C677T mutation functions at 65% activity, with homozygous 677TT just 35% activity when compared with the normal homozygous variant (C677C). The review also examines folate gene polymorphisms in relation to disease states, with cancer a predominant focus.

Breast cancer has been extensively studied in regards to MTHFR polymorphisms, with results still inconsistent. Individuals with MTHFR 677TT with high levels of folate intake showed adequate levels of methylation and hence showed modest reductions in colorectal cancer risk. Other research suggests both 677CT and 677TT polymorphisms both modestly increased colorectal cancer risk.

Studies examining the relationship between MTHFR C677T,  677TT + Leukemia are plentiful but contradictory, with results mainly showing either no significant relationship found, or a decreased susceptibility to Leukemia with either mutation.

The majority of studies completed on Chinese, Italian and Mexican populations found the MTHFR 677TT mutation to be a strong risk factor for gastric cancer.

In relation to other disease states, numerous studies show the relationship between high maternal homocysteine and the increased risk of Neural Tube Defect development in their offspring. Furthering childhood disabilities, studies have shown links between the C677T mutation and an increased risk of Downs Syndrome in offspring.

Links between MTHFR C677T and depression have also been made.
Nazki et al (2014) concluded by stating the importance of folate for DNA synthesis and methylation, and the broad reaching effects this has in body.

In accordance with the viewpoint that genes are influenced by our diet + environment, many studies are able to link a correlation with MTHFR or folate with a disease process or disability, but find it hard to pinpoint them as sole risk factors for a disease.

Article Here

 

 

February 4, 2014
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