Evaluating the Association Between Genetic Polymorphisms Related to Homocysteine Metabolism and Unexplained Recurrent Pregnancy Loss in Women

Abstract

Objective To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homocysteine metabolism-related genes in women. Materials and Methods A case–control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18–35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphism. Results The MTHFR C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference (p > 0.05). MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25–35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8–55.53; p = 0.008) when participants had more than the 3 variant loci. Conclusion The MTHFR C677T polymorphism was a risk factor for URPL, and determining the MTHFR C677T polymorphism had a potential prediction of URPL risk. Moreover, the MTHFR C677T and MTHFR A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms.

Analysis of risk factors and pregnancy outcomes in pregnant women with subchorionic hematoma

“…Increased risk of thrombosis. [12] This study found that the levels of PS activity and AT-III were lower in the SCH group compared to the normal control group. Additionally, the HCY level was higher in the SCH group than in the control group.…”

Understanding recurrent pregnancy loss: recent advances on its etiology, clinical diagnosis, and management

“…It is important to note that thrombosis or occlusion of placental vessels may decrease placental perfusion, which may contribute to adverse pregnancy outcomes including RPL [ 78 ]. Notably, several inherited variants in three thrombophilic factors, such as factor V gene, homocysteine metabolism associated enzymes ( MTHFR , MTR and MTRR ), and prothrombin gene ( PTG ), have been extensively investigated for their associations with RPL [ 79 , 80 ]. FVL , a missense mutation in the factor V gene (p.R506Q), is the most extensively studied thrombophilic variants in patients with RPL.…”

“…[ 100 ] have shown that heterozygous women for MTRR c.66 A > G show a higher RPL risk in Chinese population. However, the susceptibilities of MTR c.2756 A > G and MTRR c.66 A > G to RPL were not replicated in Vietnamese population [ 80 ].…”

Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update

“…Recurrent pregnancy loss (RPL) is defined by the American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) as the loss of two or more pregnancies before 20–24 weeks of gestation, including both embryonic and fetal losses [ 49 ]. Anatomical malformations, immunological illnesses, chromosomal errors and genetic polymorphisms, lifestyle variables, and thrombophilic gene polymorphisms have all been proposed as susceptibility factors that raise the likelihood of pregnancy loss in otherwise healthy women [ 4 , 36 ]. On the other hand, routine clinical evaluations leave roughly half of the couples unidentified [ 44 ].…”