title: Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.
abstract: BACKGROUND
  Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII) deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size.
  
  
  RESULTS
  We conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA) activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37-5.85). The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85-101% was predictive of subsequent miscarriage.
  
  
  CONCLUSIONS
  Low FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Asano
authors.affiliation: Occupational and Environmental Health, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ebara
authors.affiliation: Department of Biochemistry II, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Yamada-Namikawa
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: Nobuhiro
authors.initials: N
authors.lastname: Suzumori
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 Biochemistry II, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugiura-Ogasawara
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000328:Adult; D015331:Cohort Studies; D005174:Factor XII / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000235:genetics; D055815:Young Adult
chemical_list: D005174:Factor XII