Single Gene Abnormality Elevates Recurrent Miscarriage Risk

Researchers determine that recurrent miscarriage risk is elevated in women who carry the ACE I/D polymorphism.

Recurrent miscarriage is an emotionally devastating problem affecting one in 20 couples, especially prevalent. The condition is often the result of several factors, and researchers have already identified numerous causes, including chromosomal abnormalities, endocrine dysfunction, immune disorders, inherited thrombophilias, lifestyle factors, maternal infections, and uterine abnormality. Nevertheless, for most women with recurrent miscarriage, the cause is never discovered.

Several gene polymorphisms affect placental vasculature and circulation, and thus, they may increase the risk of recurrent miscarriage. Angiotensin-converting enzyme (ACE) in particular affects vascular structure and placental function, and its role in blood pressure regulation and electrolyte balance is well documented. Therefore, ACE abnormalities could result in fetal loss or recurrent miscarriage.

The human ACE gene, which is located on chromosome 17q23, is subject to insertion/deletion polymorphism, and humans can have one of three genotypes: DD and II homozygotes and ID heterozygotes. Particularly, the ACE I/D polymorphism is associated with increased risk of thrombotic disorders such as venous thromboembolism, stroke, and coronary artery disease.

Modified ACE expression may result in pregnancy loss, and ACE I/D polymorphism may be a susceptibility factor that increases the risk of recurrent miscarriage. However, studies examining this possibility have not been structured as robustly as necessary to provide definitive proof. Consequently, researchers recently published a meta-analysis of published data investigating the association between ACE I/D polymorphism and recurrent miscarriage risk. Using this approach, they pooled the most robust data to identify patterns and create a best evidence synthesis.

The researchers found that recurrent miscarriage risk was elevated in women who carry the ACE I/D polymorphism, with an odds ratios ranging from 1.43 to 1.90. The authors also examined allele frequencies by ethnicity and found that the ACE I/D polymorphism occurred in Caucasians and East Asians at incidence rates of approximately 50 percent and 30 percent, respectively.

As a result of those findings, the meta-analysis raised questions on the need for routine screening for the presence of the ACE I/D polymorphic variant D, and the potential to improve prediction of recurrent miscarriage risk. If screening could identify women with ACE I/D polymorphic variant D, then clinicians could prescribe thromboprophylaxis to prevent further recurrent miscarriage. However, more study is needed.