The General Influence Of Folic Acid In Health And Disease Has Many Facets

Despite the fact that folate is gaining a reputation as a simple panacea for several clinical conditions, its mechanisms of action are many-fold. So what provides a link between folate nutrition/biochemistry and a diverse list of disorders such as OVD, NTD [and other mid-line defects such as cleft palate (6)], several cancers (cervical, bronchial, colon, breast, and leukemia) (7-11), dementia (15), mood disorders (12), Down's syndrome (13,14), unexlained recurrent early pregnancy loss and preeclampsia (16,17)? The answer would seem to be that these conditions can be modulated by either (1) folate nutritional status, (2) common allelic variation in genes coding for folate-dependent enzymes (particularly common SNPs of the Hcy remethyl-ation (methionine) cycle), (3) altered gene expression, or (4) impaired nucleic acid elaboration linked to folate metabolism.

A detrimental permutation of these and as-yet undiscovered factors probably elicits a threshold effect on the occurrence of many of these serious conditions.

Birth Defects

Neural tube defects are among the commonest of all congenital malformations. The predominant types of NTD are spina bifida and anencephaly which have a prevalence of about 0.1% and 0.5% in the United States and the United Kingdom, respectively (68). Randomized trials (1,69,70) verified early work that showed periconceptional folic acid prevents NTD pregnancy (71,72), although the exact nature of the protective mechanism remains unclear. It has become well established that the etiology of NTD is multifactorial, with both gene and environment playing critical roles. Folate is the best known environmental factor, although low vitamin B12 levels have also been implicated in NTD pregnancy (73,74).

At the gene level, molecular biological studies also implicate a number of SNPs in the aetiology of these devastating birth defects. In particular,

Hcy Values (Median and IQR) for Each Female Group (Thromboembolic and Nonthromboembolic Vascular Patients, NTD Mothers and Matched NTD Controls) on the Basis of C677T Genotype

CC CT TT

NTD control mothers

CC CT TT

NTD control mothers

Median homocysteine (|imol/L)

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