Folate status, homocysteine metabolism, and methylene tetrahydrofolate reductase genotype in rural South African blacks with a history of pregnancy complicated by neural tube defects

The birth incidence of neural tube defects (NTDs) in South Africa is threef old to sixfold higher in rural compared with urban blacks. We investigated whether folate deficiency and aberrant homocysteine metabolism could explai n the high NTD incidence in rural black populations, Plasma folate and tota l homocyst(e)ine (tHcy) concentrations were determined in apparently health y rural black women (n = 107), rural black women with a history of pregnanc y complicated by NTDs (n = 54), and urban blacks (n = 101). Methionine load tests were performed on the 54 women with a history of NTD-affected pregna ncy and 54 controls matched for age and body mass. The presence of the 677C --> T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene wa s investigated in both groups by a polymerase chain reaction (PCR) of genom ic DNA and Hinfl digestion of the PCR product. Apparently healthy urban bla ck women (n = 101) had a lower (P <.001) plasma folate concentration compar ed with rural black women (n = 107). Women with a history of NTD-affected p regnancy did not differ significantly from controls with respect to plasma folate, fasting homocyst(e)ine, methionine, and the post-methionine load in crease in plasma homocyst(e)ine, More than 50% of both of the latter groups had a post-methionine load increase in plasma tHcy less than the fifth per centile as observed in a healthy white control group. No homozygotes for th e 677C --> T mutation in the MTHFR gene were found in black mothers with NT D-affected offspring or controls. It is concluded that black urbanization i s characterized by a diminished folate status that is paradoxically associa ted with a lower NTD birth incidence. Homozygosity for the 677C --> T mutat ion in the gene coding for MTHFR does not constitute a genetic risk factor for NTDs in blacks. No aberrant homocysteine metabolism could be demonstrat ed in black women with NTD-affected pregnancies. Copyright (C) 1999 by W.B. Saunders Company.