Genetic polymorphisms of the cobalamin transport system are associated with idiopathic recurrent implantation failure

Abstract

Purpose Vitamin B12 (cobalamin, Cbl) plays a role in the recycling of folate, which is important in pregnancy. Transcobalamin II (TCN2) and transcobalamin receptor (TCblR) proteins are involved in the cellular uptake of Cbl. TCN2 binds Cbl in the plasma, and TCblR binds TCN2-Cbl at the cell surface. Therefore, we investigated the potential association between polymorphisms in Cbl transport proteins, TCN2 and TCblR, and recurrent implantation failure (RIF) susceptibility. Methods The genotypes of TCN2 67A>G, TCN2 776C>G, and TCblR 1104C>T were determined for RIF patients and healthy controls using a polymerase chain reaction restriction fragment length polymorphism assay. Additionally, statistical analysis was performed to compare the genotype frequencies between RIF patients and controls. Results The TCN2 67 polymorphism AG type was associated with RIF risk. Some allele combinations that contained the TCN2 67 polymorphism G allele were associated with increased RIF risk, whereas other allele combinations that contained the TCblR 1104 polymorphism T alleles were associated with decreased RIF risk. In genotype combination analysis, two combinations containing the TCN2 67 polymorphism AG type were associated with RIF risk. Conclusion Our study showed that the polymorphisms of TCN2 and TCblR are associated with RIF and are potential genetic predisposing factors for RIF among Korean women. Additionally, our findings support a potential role for TCN2 and TCblR in RIF among Korean women. However, further studies are required to investigate the role of the polymorphisms in those proteins and RIF because the roles of the TCN2 and TCblR polymorphisms in RIF are not clear.

Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter

“…The potential role of TCN2 in the transport of B12 from the mother to the foetus was reported in pregnant adolescents, where higher placental TCN2 expression was associated with higher cord blood B12 concentrations [ 5 ]. The transcobalamin receptor (CD320) is known to be expressed in actively dividing cells [ 6 ] and required for the uptake of TCN2-bound B12 [ 7 ]. Studies have also shown that CD320 knockout mice have B12 deficiency and have behavioural abnormalities, macrocytic anaemia, infertility and hypomethylation of DNA in the brain [ 8 ].…”

Whole exome sequencing, a hypothesis-free approach to investigate recurrent early miscarriage

“…Kim et al reported a possible relationship between REM and TCN2 rs9606756 among Korean women (P=0.019 OR: 2.918; 95% CI 1.193-7.137) whereas Hashemi et al did not find any association between REM and TCN2 rs180119 (a common polymorphim) or TCN2 rs2336573 among Iranian women. More recently, Park et al reported an increased risk for recurrent implantation failure after in vitro fertilization for carriers of the TCN2 rs9606756 G allele (P=0.025 OR: 4.732; 95% CI 1.220-18.356) (Park et al, 2019).…”

Impaired myeloid-derived suppressor cells are associated with recurrent implantation failure: A case-control study

“…Numerous studies have found that the identi able causes include parental chromosomal abnormalities, defective embryonic development, uterine anatomic anomalies, and poor endometrium [3][4][5][6]. Nevertheless, more and more researches have focused on the immunological aspects, especially a failure to establish maternal-fetal immunotolerance for successful implantation.…”