Annexin A5 haplotype M2 is not a risk factor for recurrent spontaneous abortion in Northern Europe: is there sufficient evidence?

The M2 haplotype of the annexin A5 gene is a well-recognized predisposition factor for recurrent spontaneous abortion (RSA). A recent publication by Nagirnaja et al. (2015) in PLoS One discusses the risk role of the M2 haplotype for RSA in cases compared with controls of North European extraction and arrives at a negative result. As a number of previous and fairly recent studies have supported the proposed involvement of the M2 haplotype in the cause of idiopathic RSA, this commentary aims to highlight problematic issues in the above publication. It is the opinion of the authors that the study by Nagirnaja et al. (2015) does not generate adequate proof of the absence of RSA risk, attributable to carriage of the M2 haplotype.