Association of ACE I/D polymorphism and recurrent miscarriages in an Italian population with a pre-modern reproductive pattern

Angiotensin I-converting enzyme (ACE), in addition to its role in the renin angiotensin system, has a physiological function in the fibrinolysis pathway, the accurate control of which is critical for the normal development of pregnancy. Recently, the ACE I/D polymorphism was found to be associated with recurrent spontaneous miscarriages (RM). The present study analysed the relationship between ACE I/D polymorphism and the number of spontaneous miscarriages, the number of pregnancies and the number of children in a sample of 88 Italian women born before 1930, with a pre-modern reproductive behaviour. The ACE DD genotype was more prevalent among women with RM (p = 0.02). However, the women carrying the DD genotype not only had the highest number of miscarriages (p = 0.03), but also the highest number of pregnancies with an eventual complete fertility (children no = 4.4), similar to that of women carrying the other ACE genotypes. In contrast, published data on contemporary women with RM seem to indicate that the DD genotype could now be associated with a reduced reproductive success compared to the other ACE genotypes. It is suggested that this phenomenon may be the effect of the interaction between ACE genotypes and contemporary reproductive behaviours (delay in childbearing, below-replacement fertility).