Polymorphisms in genes involved in folate metabolism and orofacial clefts

Background

Orofacial clefts (OFCs) are one of the most common birth defects in humans. Maternal use of folate antagonists including dihydrofolate reductase inhibitors has been associated with a higher risk of OFCs thus suggesting that folate-related metabolism and associated genes may be involved in pathogenesis of OFC. The association between folate intake and risk of OFCs however is inconsistent.

Objective

To review the published evidence that polymorphisms in genes that affect folate metabolism are associated with an increased risk of OFCs.

Methods

We reviewed articles published up until October 2010, on polymorphisms of genes related to folate and homocysteine metabolism and their associations with OFCs. Articles were identified via Medline searches.

Conclusions

No consistent evidence emerged of a strong association between risk of OFCs and any known gene related to folate metabolism. Further, recent genome-wide association studies have not identified associations between OFCs and folate-related genes. Further studies are warranted to determine whether gene–environment interactions, including gene–nutrient interactions and epigenetic modifications of genes affect the risk of OFCs.