Transferrin and HLA: spontaneous abortion, neural tube defects, and natural selection.

We report evidence that transferrin C3, a gene present in 9 to 10 per cent of whites, is associated with recurrent spontaneous abortion (P = 0.001) and that maternal transferrin genotype has an effect on the transmission ratio of the common transferrin genes (C1, C2, and C3) from heterozygous fathers to normal offspring (P less than 0.002). The effect of maternal genotype on paternal gene transmission is an unusual example of the operation of selection in the human reproductive process. This effect, together with the separate evidence for association of the transferrin C3 allele with spontaneous abortion, indicates that transferrin is a second marker (in addition to HLA) of genes important in reproduction. On the basis of comparison of the frequencies of transferrin (chromosome 3) and HLA (chromosome 6) mating types in 348 control couples and in 81 couples who had had a child with a neural tube defect, we hypothesize that some combinations of maternal and fetal genes on these two chromosomes may be associated with neural tube defects.