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Genetic Polymorphisms Related to Recurrent Pregnancy Loss

By LabMedica International staff writers
Posted on 13 Jun 2022
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Image: The DTprime real-time PCR instrument is used for qualitative and quantitative analysis of DNA and RNA targets (Photo courtesy of DNA-Technology)
Image: The DTprime real-time PCR instrument is used for qualitative and quantitative analysis of DNA and RNA targets (Photo courtesy of DNA-Technology)

Recurrent pregnancy loss (RPL) is defined as experiencing two or more spontaneous miscarriages occurring within 20 weeks of gestation and was reported to affect up to 1%–5% of women of reproductive age seeking pregnancy. The causes are unidentifiable in 50% of the patients who are classified as experiencing unexplained recurrent pregnancy loss (URPL).

It has been reported that there exists an association between URPL and genetic polymorphisms related to inherited thrombophilic factors such as Factor V Leiden (FV), plasminogen activator inhibitor-1 (PAI-1), and homocysteine metabolism amongst others. Homocysteine is an amino acid made from methionine by losing its terminal methyl group, and the remethylation generating methionine requires folate and vitamin B12.

Clinical Embryologists and their colleagues at the Vietnam Military Medical University (Hanoi, Vietnam) enrolled in a case–control study 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 study was undertaken from May 2019 to May 2021.

Genomic DNA was extracted from peripheral blood with anticoagulant with the E.Z.N.A. Blood DNA Mini Kit (Omega BIO-TEK, Norcross, GA, USA). The polymorphisms of MTHFR, MTR, and MTRR were detected by high resolution melting technology with the Folate Metabolism REAL-TIME PCR Genotyping Kit (DNA-Technology, Moscow, Russia). The reactions were carried out on the DNA-Technology DTprime 5M1 real-time system.

The investigators reported that the MTHFR C677T polymorphism had significantly correlation with URPL. The frequency of the 677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group. However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference. MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR = 9.0), while the risk increased 10.0-fold (OR = 10.0) when participants had more than the three variant loci.

The authors concluded that 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. The study was published on June 7 2022 in the journal The Application of Clinical Genetics.

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