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Genotyping analysis of protein S-Tokushima (K196E) and the involvement of protein S antigen and activity in patients with recurrent pregnancy loss<Abstract of dissertation>

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Nagoya City University Academic Repository

学 位 の 種 類 博士 (医学) 報 告 番 号 甲第1598号 学 位 記 番 号 第1136号 氏 名 松川 泰 授 与 年 月 日 平成 29 年 9 月 28 日 学位論文の題名

Genotyping analysis of protein S-Tokushima (K196E) and the involvement of protein S antigen and activity in patients with recurrent pregnancy loss

(不育症におけるプロテイン S 欠乏症とプロテイン S 徳島)

European Journal of Obstetrics & Gynecology and Reproductive Biology. Vol.211, P.90-97,2017

論文審査担当者 主査: 齋藤伸治

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Preston et al. indicated that Protein S (PS) deficiency was associated with stillbirths but not

miscarriages. The PS-Tokushima missense variant was reported to serve as a genetic risk factor

for deep vein thrombosis in the Japanese population. A previous cross-sectional study showed

no increase in the prevalence of PS-Tokushima in patients with recurrent early pregnancy loss or

in patients with intra uterine fetal death and/or fetal growth restriction. There has been limited

number of prospective studies examining the pregnancy outcome in patients with both a PS

deficiency and recurrent pregnancy loss (RPL). We examined the association between PS

deficiency, PS-Tokushima and RPL. The study group consisted of 355 Japanese women with

two or more consecutive pregnancy losses and 101 parous women. The frequency of

PS-Tokushima and the subsequent live birth rate in relation to a PS deficiency defined as low

PS-specific activity (total PS activity/ total PS antigen) and the presence of PS-Tokushima were

examined. There was no significant difference in the frequency of PS-Tokushima between

patients and controls. The 8 patients carriers of PS-Tokushima variant were capable of a

subsequent live birth without the use of heparin. There was no significant difference in

subsequent live birth rates between patients with low or normal PS-specific activity/PS activity

without heparin prophylaxis after excluding miscarriages caused by an abnormal embryonic

karyotype using multivariate logistic regression analysis. There was no association between

PS-Tokushima and RPL and a PS deficiency or low PS activity was shown not to serve as a

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