Nonsynonymous mutations in three anticoagulant genes in Japanese patients with adverse pregnancy outcomes

Hereditary thrombophilias may associate with uteroplacental thrombosis leading to adverse pregnancy outcomes. The present study was conducted to reveal the frequency of the low-frequency thrombophilic protein S K196E mutation, as well as the frequency of very rare nonsynonymous mutations in protein S, protein C, and antithrombin genes, in patients with adverse pregnancy outcomes.

We enrolled 330 Japanese patients with adverse pregnancy outcomes and divided them into 233 patients with two or more miscarriages and 114 patients with fetal growth restriction (FGR) and/or intrauterine fetal death (IUFD); 17 patients belonged to both groups. We sequenced the entire coding regions of three anticoagulant genes in all 330 patients.

We found that protein S K196E mutation was identified in 4 out of 233 patients with recurrent miscarriage and in 2 out of 114 patients with FGR and/or IUFD. The frequencies of this mutation in these patient groups were not different from that in a Japanese general population. Very rare nonsynonymous mutations were identified in 3.3% (11 out of 330) of patients with adverse pregnancy outcomes.

Although the low-frequency protein S K196E mutation can increase the risk for venous thromboembolism, it did not increase the risk for adverse pregnancy outcomes even in Japanese.