Friday May 30 1:39 PM EDT

Mutation May Cause Low Folic Acid

NEW YORK (Reuters) -- As many as 15% of people may have a genetic variation causing a deficiency in the vitamin folic acid, even if they are meeting nutritional guidelines for the vitamin, according to results of a new study.

"These results suggest that a substantial minority of people in general populations may have increased folate needs," write the team of Irish and America researchers.

Low levels of folic acid, or folate, have been linked to anemia and to a class of serious birth defects called neural tube defects. Folate deficiency also may increase the risk of coronary artery disease and stroke.

If this genetic variation is as common as the study results indicate, and if there are similar genetic variations affecting other important nutrients, current dietary guidelines may lose their relevance, say the authors of a study published in this week's issue of The Lancet.

"Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming 'normality' for nutrient requirements in any general population," write the study authors.

Neural tube defects, affecting the brain or spinal cord, occur in about 1 out of 1,000 pregnancies in the U.S. each year.

One of the most common neural tube defects is spina bifida, in which part of the spinal cord protrudes from the spinal column, causing paralysis. Another is anencephaly, a fatal condition in which the fetal brain fails to develop normally.

A few years ago, a research team led by Dr. Anne Molloy, of Trinity College, Dublin, identified a mutation in the gene for a particular enzyme, called 5,10 methylenetetrahydrofolate reductase. The enzyme activates folate within the cells, and a mutation in the gene makes the enzyme much less effective.

People with two copies of the abnormal gene had a higher risk of having a neural tube defect, compared with people who had two normal genes or just one copy of the abnormal gene.

About 5% to 15% of people have two copies of the abnormal gene, a figure that varies with the population being studied.

The researchers went on to look for the mutation in blood samples from Irish women, a population in which there is a relatively high rate of neural tube defects. Twenty of 242 pregnant women and 41 of 318 non-pregnant women tested had two copies of the abnormal gene.

Women with two copies of the abnormal gene also had lower levels of folate in their red blood cells than other women. This suggests, but does not prove, that the women with two abnormal genes have a higher folate requirement than the rest of the population, the authors say.

Men with the same genetic variation might have an increased risk of heart disease, stroke and colon cancer, according to Dr. James L. Mills, one of the U.S. members of the research team and chief of the pediatric epidemiology section at the National Institute of Child Health and Human Development (NICHD).

The study "challenges the assumption underlying the recommended daily allowance (RDA) -- that virtually everyone can take the same amount of a vitamin and do fine," Mills stated in a press release from the NICHD.

The current RDA for folate is 400 micrograms per day for pregnant women, 180 micrograms for other adult women, and 200 micrograms for adult men.

The RDA was created to reflect the dietary requirements for an average person. "If genetic variants that cause altered nutrient status are common, as this study suggests, there may be no such thing as a 'normal' population with respect to nutrient requirements," the researchers concluded. SOURCE: Lancet (1997;349:1591-1593)