title: Further insights into the role of the annexin A5 M2 haplotype as recurrent pregnancy loss factor, assessing timing of miscarriage and partner risk.
abstract: OBJECTIVE
  To study the influence of M2/ANXA5 for recurrent pregnancy loss (RPL), according to the timing of miscarriages and assess the male partner risk.
  
  
  METHODS
  Genetic association study.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Female patients from two academic centers in Germany and Bulgaria with two or more unexplained miscarriages were selected for this study. Male partners were available for a part of the German sample. Population controls were recruited from healthy individuals of respective populations.
  
  
  METHODS
  None.
  
  
  METHODS
  Incidence of M2 carriage and odds ratios were calculated between patient and control groups, and RPL risk was evaluated.
  
  
  RESULTS
  The M2 haplotype in ANXA5 was associated with greater overall RPL risk in German and in Bulgarian women, and a trend of higher prevalence was seen for male partners of German RPL patients. The highest relative risk of M2 carriage was observed in women of both populations with "early" fetal losses between the 10th and 15th gestational weeks, which was significant in the meta-analysis.
  
  
  CONCLUSIONS
  M2 carriage seems to have an RPL risk role mostly for early abortions, gestational weeks 10-15. In the first phase of pregnancy this correlates with vascular remodeling to accomplish the transition from high- to low-resistance blood vessels.
authors.affiliation: Institute of Human Genetics, ZMBE and IZKF, University Clinic Muenster and University of Muenster, Muenster, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Tüttelmann
authors.forename: Petar
authors.initials: P
authors.lastname: Ivanov
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dietzel
authors.forename: Anna
authors.initials: A
authors.lastname: Sofroniou
authors.forename: Tsvetomira M
authors.initials: TM
authors.lastname: Tsvyatkovska
authors.forename: Regina S
authors.initials: RS
authors.lastname: Komsa-Penkova
authors.forename: Arseni
authors.initials: A
authors.lastname: Markoff
authors.forename: Peter
authors.initials: P
authors.lastname: Wieacker
authors.forename: Nadja
authors.initials: N
authors.lastname: Bogdanova
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics; D000022:Abortion, Spontaneous / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017304:Annexin A5 / Q000235:genetics*; D002031:Bulgaria / Q000453:epidemiology; D016022:Case-Control Studies; D005220:Fathers; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D005865:Gestational Age; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009035:Mothers; D016017:Odds Ratio; D010641:Phenotype; D011247:Pregnancy; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D017304:Annexin A5
keywords: ANXA5; M2/ANXA5; annexin A5; recurrent pregnancy loss; risk factor