Abstract
BACKGROUND: Annexin A5 (ANXA5) haplotypes can increase the risk of recurrent pregnancy loss (RPL). This study aimed to investigate the effect of ANXA5 haplotypes on ANXA5 expression in patients with RPL. METHODS: Female subjects with RPL, parous controls (those who intentionally aborted without medical conditions or complications), and population controls (normal delivery) were studied. Real-time polymerase chain reaction was carried out to evaluate ANXA5 expression in the placenta and peripheral blood. Western blotting and immunohistochemistry were used to assess ANXA5 protein expression. The luciferase assay was performed to detect the effect of M1 and M2 haplotypes on transcription efficiency of the ANXA5 promoter. RESULTS: We found that the percentage of the M2 carrier was highest in the RPL group. ANXA5 expression in the placenta and peripheral blood in subjects with RPL was significantly inhibited. Furthermore, ANXA5 expression in subjects carrying the M2 haplotype was remarkably suppressed compared with that in carriers of other haplotypes. Finally, the M2 haplotype decreased the transcription efficiency of the ANXA5 promoter. CONCLUSION: Our findings show that ANXA5 expression is decreased in carriers of the M2 haplotype and that M1/M2 haplotypes in the ANXA5 gene are associated with an increased risk of RPL.