Reiko Neki1, Toshiyuki Miyata2, Tomio Fujita3, Koichi Kokame4, Daisuke Fujita5, Shigeyuki Isaka6, Tomoaki Ikeda7, Jun Yoshimatsu7. 1. Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. Electronic address: rneki@ncvc.go.jp. 2. Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. Electronic address: miyata@ncvc.go.jp. 3. Department of Maternal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan. 4. Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. 5. Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka, Japan. 6. Department of Obstetrics and Gynecology, Kaizuka City Hospital, Kaizuka, Osaka, Japan. 7. Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Abstract
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.
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.
Authors: Matt Halvorsen; Ying Lin; Barbara A Sampson; Dawei Wang; Bo Zhou; Lucy S Eng; Sung Yon Um; Orrin Devinsky; David B Goldstein; Yingying Tang Journal: EBioMedicine Date: 2017-01-31 Impact factor: 8.143