title: Genotyping analysis of protein S-Tokushima (K196E) and the involvement of protein S antigen and activity in patients with recurrent pregnancy loss.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 carriage of PS-Tokushima were examined.
  
  
  CONCLUSIONS
  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 reliable clinical predictor of subsequent miscarriage.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsukawa
authors.affiliation: Department of Obstetrics and Gynecology, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Asano
authors.affiliation: Research and Development, Shino-Test Corporation, Kanagawa, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsuda
authors.affiliation: Nagasaki International University, Nagasaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuma
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Tamao
authors.initials: T
authors.lastname: Kitaori
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kinue
authors.initials: K
authors.lastname: Katano
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ozaki
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan. Electronic address: og.mym@med.nagoya-cu.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugiura-Ogasawara
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology* / Q000235:genetics; D000328:Adult; D000483:Alleles; D001723:Birth Rate; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D017293:Protein S / Q000235:genetics*; D018455:Protein S Deficiency / Q000150:complications* / Q000235:genetics
chemical_list: D017293:Protein S; C083863:protein S Tokushima
keywords: Lupus anticoagulant; Protein S; Protein S-Tokushima; Recurrent pregnancy loss