Paternal HLA genotype and offspring sex ratio

For twenty years, W.H. James has been proposing that the sex hormone level of both parents could control at least a quota of the secondary sex ratio v ariation at the time of conception. Observations supporting this hypothesis have come from investigations on some diseases related to the human leukoc yte antigen (HLA). In the present study on 1102 healthy Italian families, w e investigated the potential effect on the offspring sex ratio of HLA-B all eles on the basis of a genetic model. We defined three subsets of HLA-B all eles and hypothesized a locus (L) with three alleles, L-H, L-N, L-B15, on t he basis of the positive, neutral, or negative effect on the testosterone l evel. According to the genetic model and the dominance relation L-H > L-B15 > L-N, six genotypic and three phenotypic classes (H. N, B15) can be expec ted. We found a significantly high number of daughters (66%) born to father s carrying the B15 phenotype. This result suggests an effect of the HLA-B15 allele on the secondary sex ratio, mediated by a low testosterone level.