ANXA5 gene M2 haplotype

The ANXA5 gene encodes the placental anticoagulant protein Annexin5. Current research shows that the M2 haplotype of the ANXA5 gene may be associated with recurrent reproductive loss and obstetric complications due to placental disorders.  The mixture of Annexin5 produced by the foetus and mother is deposited on the surface of the villi of the placenta and prevents blood clots from forming there; the blood clots can reduce the quality of foetal nutrition and lead to complications during the pregnancy. Annexin5 production is influenced by hereditary changes (variants) in gene composition. Four tested variants in the regulatory region of the ANXA5 gene (rs112782763, rs28717001, rs28651243 and rs113588187) are significant and are inherited simultaneously as the so-called ANXA5 haplotype. The risk combination of these variants forms the M2 haplotype ANXA5. Transcription of the genetic code into the structure of Annexin5 and its formation may be slowed down in M2/ANXA5 haplotype carriers. The testing is based on real-time PCR. This method enables monitoring of the progress of the amplification reaction at any point. Each individual cycle has the same properties as classical PCR, i.e. denaturation of double-stranded DNA, primer mounting, chain extension by Taq DNA polymerase. When annealing, not only the appropriate primers are used, but also probes (specific DNA oligonucleotide sequences) with fluorophores. Detection selectivity is ensured by specific probes.

Before initiating combined oral hormonal contraception and/or hormone replacement therapy (HRT) in women with a positive personal history of TEN or a positive family history of TEN in first-degree relatives (mother, father, siblings and children), in women with primary sterility or recurrent abortions in the first trimester of pregnancy or in any foetal loss after this period of gestation, in pregnant women with a positive personal or family history of TEN (see Section 1) or in severe forms of preeclampsia, foetal retardation, placental abruption and stillbirth, in persons with a history of idiopathic TEN to determine the causative cause and to decide on the duration of anticoagulant therapy. If thrombophilic mutations are positively detected, it is advisable to perform these tests in first-degree relatives. In children older than 12 years, unless there are other reasons to perform this testing sooner, or from another indication after examination in the Thrombotic Centre, or indications are part of the Recommended Practice of the Society for Medical Genetics and Genomics, J. E. Purkyne Czech Medical Society – see https://slg.cz/doporuceni/trombofilni-stavy/