Associations Between the Endothelial Nitric Oxide Synthase Gene (NOS3), Reproductive Behaviors, and Twinning

Fertility decline in industrialized nations, fuelled by increased educational opportunity and delayed marriage/childbearing, is a driving force in reshaping contemporary population structure. These same forces have contributed to an increase in twinning, due to fertility drugs, but a possible decline in natural dizygotic twinning. Twinning has been linked to elevations in testosterone and age-related increases in follicle-stimulating hormone. Using data from 473 females, we examined the role of the regulatory gene for nitric oxide synthase (NOS3) in fertility-related events and in the vulnerability to preeclampsia, or pregnancy-induced hypertension (PIH). We found that the 2-allele of a biallelic marker for this gene was associated with increased risk of PIH, with testosterone, with LH/FSH ratio, and with earlier age at menarche. Subsequent studies of the mothers of twins revealed that the NOS3 2-allele was associated with earlier maternal age at the birth of the twins, less education, and increased monozygotic twinning rate among females with birth ages <30. Additionally, 2-allele carriers evaluated by the multiphasic personality questionnaire had elevated scores for aggression and decreased scores for achievement orientation. These data suggest that, other events equal, the NOS3 2-allele carriers would outproduce NOS3 1-allele carriers, eventually threatening the viability of the 1-allele. However, prior to recent advances in medicine, preeclampsia, linked to the 2-allele, is thought to have had a roughly 40% rate of maternal/fetal mortality, balancing the selective advantages otherwise conferred upon the 2-allele.