A sex-specific difference in homozygosity for HLA-DR53 in newborns

Homozygosity for HLA-DR53 confers increased susceptibility to major forms of leukemia. In childhood leukemia, this influence is male-specific. Two separate studies have shown a male-specific increase in the homozoygosity rate for HLA-DR53 in healthy adults. This finding was attributed to possible preferential transmission of HLA-DR53 towards male offspring. If this is the case, the consequences of such a prenatal event should be evident in the newborn population. The present study investigated HLA-B and -DQA1 genotype frequencies in a sample of 134 newborns (73 boys, 61 girls) in Turkey. Restriction fragment length polymorphism (RFLP) analysis showed a homozygosity rate of 8.2 percent for HLA-DR53. Nine of 11 homozygotes were boys and the sex-specific rates were 12.3 percent vs 3.3 percent in boys and girls, respectively (p = 0.05). The DR53 homozygosity rate in males was higher than the expected rate (p = 0.02). These findings suggested a prenatal mechanism behind the excess of DR53 homozygotes in the male population. To maintain equilibrium, this excess seems to be eliminated postnatally. This model also explains how a deleterious genotype escapes natural selection.