Anxa5
The Annexin A5 (or annexin V) ANXA5 gene on chromosome 4 encodes is a cellular protein in the annexin group, which is also known as placental protein 4 (PP4). The function of the protein is unknown; however, based on in vitro studies, annexin A5 has been proposed to play a role in the inhibition of blood coagulation by competing for phosphatidylserine binding sites with prothrombin and also to inhibit the activity of phospholipase A1.Wikipedia
In 2007, a publication reported that a particular haplotype of the ANXA5 gene was associated with infertility based on up to 4x higher odds of recurrent pregnancy loss in a German population of women. This haplotype was called the M2 haplotype, and it was based on all four minor alleles at the following SNPs [PMID 17339269
]:
- rs112782763: -19G>A
- rs28717001: 1A>C
- rs28651243: 27T>C
- rs113588187: 76G>A
[Note that the minor alleles listed above are based on the (reverse/minus) orientation of the cDNA, whereas the orientation for these four SNPs in SNPedia and dbSNP are based on the forward/plus strand.]
Subsequent attempts to replicate the association between the M2 haplotype and recurrent pregnancy loss (or infertility) have met with mixed success. In particular, a 2015 study of women from Estonia and Denmark found no association between the M2 haplotype and recurrent pregnancy loss, and the authors stated that the "high prevalence of the M2 haplotype among fertile controls and world-wide populations is inconsistent with the previously proposed severe impact on early pregnancy success".[PMID 26135579]
