Genetics of signal transduction and the effect of maternal smoking on sex ratio of offspring

We investigated the possible effects of ACP1 on the relationship between maternal smoking and sex ratio of offspring. ACP1 is a highly polymorphic enzyme involved in signal transduction of growth factors, glucose metabolism, flavoenzyme activity, and T-cell activation. A sample of 357 consecutive newborns from the population of Rome and a sample of 362 consecutive newborns from the population of Penne were studied. In both populations, among female newborns from smoking mothers there was a higher proportion of the A phenotype (associated with the lowest enzymatic activity) and a lower proportion of carriers of the *C allele (associated with the highest enzymatic activity) compared to female infants from nonsmoking mothers. In newborns from smoking mothers there was a positive correlation between sex ratio and ACP1 activity. The data suggest intrauterine selection induced by smoke that is dependent on sex and the ACP1 genotype of the zygote. It has been shown that low ACP1 activity is associated with high activity of the flavoenzyme glutathione reductase, an enzyme that has an important role in the protection of cellular structures from oxidative damage. Thus, the A phenotype may have a protective effect against oxidative damage by cigarette smoking through an enhancement of glutathione reductase activity. (C) 2004 Wiley-Liss, Inc.