Recurrent pregnancy loss and its relation to combined parental thrombophilic gene mutations

Genet Test Mol Biomarkers. 2012 Apr;16(4):279-86. doi: 10.1089/gtmb.2011.0191. Epub 2011 Nov 2.


Background and aim: Recurrent pregnancy loss (RPL) is a heterogeneous disorder that has been associated with antiphospholipid syndrome and other prothrombotic parameters. We aimed to investigate the prevalence of 12 thrombophilic gene mutations in RPL couples in the current results.

Method: In a total of 543 Turkish women with RPL and 327 of their male partners (870 individuals with RPL), and a control group of 106 fertile couples (control) were analyzed for factor V leiden (FVL), factor V H1299R, factor II prothrombin G20210A, FXIII V34L, β-fibrinogen -455G>A, plasminogen activator inhibitor-1 (PAI-1), GPIIIa L33P (HPA-1 a/b L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q, and Apo E genes.

Results: The overall, heterozygous and/or homozygous point mutations in FVL-FVR2, ApoE2, PAI-1, MTHFR C677T-A1298C, and ACE genes were associated with RPL. There was no meaningful association between RPL and other studied genes.

Conclusion: The homozygosity of 4G in PAI-1 and MTHFR C677T genes in women with RPL, and heterozygosity of FVL, FVR2, ACE, and ApoE2 genes in both parents play crucial role in RPL and should be considered as a risk factor in RPL. Current results showed that RPL is related to combined parental (not only maternal) thrombophilic gene mutations.

MeSH terms

  • Abortion, Habitual / genetics*
  • Adolescent
  • Adult
  • Alleles
  • Apolipoprotein E2 / genetics
  • Apolipoprotein E4 / genetics
  • Factor V / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Mutation*
  • Parents
  • Plasminogen Activator Inhibitor 1 / genetics
  • Pregnancy
  • Pregnancy Complications, Hematologic / etiology
  • Pregnancy Complications, Hematologic / genetics*
  • Thrombophilia / complications
  • Thrombophilia / genetics*
  • Turkey
  • Young Adult


  • Apolipoprotein E2
  • Apolipoprotein E4
  • Plasminogen Activator Inhibitor 1
  • factor V Leiden
  • Factor V
  • Methylenetetrahydrofolate Reductase (NADPH2)