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

作者：Neki Reiko^*; Miyata Toshiyuki; Fujita Tomio; Kokame Koichi; Fujita Daisuke; Isaka Shigeyuki; Ikeda Tomoaki; Yoshimatsu Jun

来源：Thrombosis Research, 2014, 133(5): 914-918.

DOI：10.1016/j.thromres.2014.02.012

• Fetal death
• Fetal growth restriction
• Miscarriage
• Protein S
• Thrombophilia

Background: 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.
Patients and methods: 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.
Results: 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.
Conclusions: 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.

• 出版日期2014-5