GENETIC-EFFECTS ON VARIATION IN RED-BLOOD-CELL FOLATE IN ADULTS - IMPLICATIONS FOR THE FAMILIAL AGGREGATION OF NEURAL-TUBE DEFECTS

Recent studies have implicated folic acid as an important determinant of normal human growth, development, and function. Insufficient folate levels appear to be a risk factor for neural tube defects (NTD), as w ell as for several chronic diseases of adulthood. However, relatively little is known about the factors that influence folate status in the general population. To estimate the relative contribution of genetic a nd nongenetic factors to variation in folate, we have evaluated red bl ood cell (RBC) folate levels in 440 pairs of MZ twins and in 331 pairs of DZ twins. The data were best described by a model in which 46% of the variance in RBC folate was attributable to additive genetic effect s, 16% of the variance was due to measured phenotypic covariates, and 38% of the variance was due to random environmental effects. Moreover, the correlations for RBC folate in MZ co-twins (r = .46) and in repea t measures from the same individual (r = .51) were very similar, indic ating that virtually all repeatable variation in RBC folate is attribu table to genetic factors. On the basis of these results, it would seem reasonable to initiate a search for the specific genes that influence RBC folate levels in the general population. Such genes ultimately ma y be used to identify individuals at increased risk for NTD and other folate-related diseases.