Folate and homocysteine interrelationships including genetics of the relevant enzymes.
OBJECTIVE
Inadequate folate status has been linked to risk of a wide range of adverse health conditions throughout life, from birth defects and complications of pregnancy to cardiovascular disease, cancer and cognitive dysfunction in the elderly. In many instances these risks are manifested through elevated plasma homocysteine. This review focuses on current research into the contribution of genetic variability to folate status and disease predisposition.


RESULTS
Some dozen potentially important polymorphisms in folate-related genes have been examined for disease associations or for their role in determining the level of plasma homocysteine. In most instances, the effects are either modest, not significant, or undetectable. However, the mechanism by which the 677C-->T variant of methylenetetrahydrofolate reductase determines homocysteine status has become clearer with the elucidation of a critical role for riboflavin in modulating the plasma homocysteine of TT homozygotes. Moreover, several new metaanalyses have confirmed an association of this variant with vascular disease, probably through low folate status and elevated plasma homocysteine.


CONCLUSIONS
There are enormous difficulties in attempting to assess the contribution of minor genetic variability to nutrient status, against major background differences due to ethnicity, age, gender, lifestyle, dietary habits and disease status. Nevertheless, this is an important goal in the future management of chronic multifactorial disease. The present research into the genetic components of folate and homocysteine variability is paving the way towards an eventual capacity to ensure optimal folate status in every individual and, consequently, to reduce their risk of developing such diseases.
Molloy
Anne M
AM
Department of Clinical Medicine, Trinity College Dublin, Ireland. amolloy@tcd.ie
D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D006710:Homocysteine / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+) / Q000235:genetics*
D006710:Homocysteine; D005492:Folic Acid; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+)