The effect of single nucleotide genetic polymorphisms of folic acid cycle on the female reproductive system disorders

Uvarova, Marina A; Ivanov, A. V.; Dedul, A. G.; Sheveleva, T. S.; Комличенко, Э. В.

doi:10.3109/09513590.2015.1086504

Cited by 4 publications

(4 citation statements)

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“…Subsequently, SAM is first converted to S-adenosyl homocysteine and then to homocysteine. The presence of genetic polymorphisms that alter the functionality of key transport molecules and enzymes necessary for the folate/homocysteine cycle may pre-dispose individuals to genome instability, altered recombination, and abnormal segregation [50,51] .…”

Section: Discussionmentioning

confidence: 99%

Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation

Efremova

Ponomarenko

Чурносов

2022

Reproductive and Developmental Medicine

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Objective: Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation (FGR). This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of FGR. Methods: This case-control study recruited 365 women in the third trimester of pregnancy, including 122 FGR patients and 243 controls. The women were genotyped for 5 polymorphisms of the 4 folate cycle genes: MTR (rs1805087), MTRR (rs1801394), serine hydroxymethyl transferase (SHMT1; rs1979277), and TYMS (rs699517 and rs2790). The SNP × SNP interactions in the two-, three-, and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it (the model-based multifactor dimensionality reduction method). Results: Four loci of maternal folate cycle genes (rs1805087 MTR, rs2790 TYMS, rs1801394 MTRR, and rs1979277 SHMT1) were associated with FGR in 3 significant models of single nucleotide polymorphism (SNP) × SNP interactions (two-, three-, and four-locus models) (P <0.05). The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1 (1.70% of entropy), rs1805087 MTR (0.96%), and interactions between rs1979277 SHMT1 × rs1805087 MTR (-1.11%) and rs1801394 MTRR × rs1979277 SHMT1 (−0.64%). The four-locus maternal genotype combination AG rs1801394 MTRR × AA rs1805087 MTR × CT rs1979277 SHMT1 × AG rs2790 TYMS was associated with an increased risk of FGR (β = 2.69, P = 0.012). FGR-associated SNPs were correlated with the expression of 16 genes (MTR, MTRR, SHMT1, ALKBH5, CTD-2303H24.2, ENOSF1, FAM106A, FOXO3B, LGALS9C, LLGL1, MIEF2, NOS2P2, RP11-806L2.6, SMCR8, TOP3A, and USP32P2) in various tissues and organs related to FGR pathophysiology. Conclusion: SNP × SNP interactions of maternal folate cycle genes (MTR, MTRR, SHMT1, and TYMS) are associated with the development of FGR.

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Section: Discussionmentioning

confidence: 99%

Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation

Efremova

Ponomarenko

Чурносов

2022

Reproductive and Developmental Medicine

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“…SNP analysis was performed either by using a reagent kit for allele-specific PCR of Litekh Research and Production Company, Moscow, Russia, followed by electrophoretic detection (2009-2013) as described pereviously [10] or using a reagent kit for the real-time PCR and thermocycler ''DNA-Technology Prime'' production of LLC ''DNA-Technology'', Moscow, Russia (2014Russia ( -2015.…”

Section: Methodsmentioning

confidence: 99%

Toward optimal set of single nucleotide polymorphism investigation before IVF

Ivanov

Dedul

Fedotov

et al. 2016

Gynecological Endocrinology

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Background: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP. Materials and methods: During 2009-2015 in the University Hospital of St. Petersburg State University, blood samples were analyzed from 550 women with different reproductive system disorders preparing for IVF and 46 healthy women in control group. In total, 28 SNP were analyzed in the genes of thrombophilia factors, folic acid cycle, detoxification system, and the renin-angiotensin system. The method used was real-time PCR. Results: A significant increase in the frequency of pathological alleles of some polymorphisms in patients with habitual failure of IVF was shown, compared with the control group. As a result, two options defined panels for optimal typing SNP before IVF were composed. Standard panel includes 8 SNP, 5 in thromborhilic factors, and 3 in folic acid cycle genes. They are 20210 G4A of FII gene, R506Q G4A of FV gene (mutation Leiden), -675 5G44G of PAI-I gene, L33P T4C of ITGB3 gene, -455 G4A of FGB gene, 667 C4T of MTHFR gene, 2756 A4G of MTR gene, and 66 A4G of MTRR gene. Extended panel of 15 SNP also includes 807 C4T of ITGA2 gene, T154M C4T of GP1BA gene, second polymorphism 1298 A4C in MTHFR gene, polymorphisms of the renin-angiotensin gene AGT M235T T4C and -1166 A4C of AGTR1 gene, polymorphisms I105V A4G and A114V C4T of detoxification system gene GSTP. Conclusion:The results of SNP genotyping can be adjusted for treatment tactics and IVF, and also medical support getting pregnant. The success rate of IVF is increased as the result, especially in the group with the usual failure of IVF.

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“…Wherein, the presence of SNP pathological alleles in the clotting factors genes, the renin-angiotensin system genes, the detoxification system genes and the folic acid cycle genes is quite significant. For a fairly narrow group of women with a habitual failure of IVF the polymorphisms C677T of the MTHFR gene and A66G of the MTRR gene exert the greatest influence as well as SNP A2756G of the MTR gene in combination with pathological alleles in the MTHFR and MTRR genes even as heterozygote [2].…”

Section: Introductionmentioning

confidence: 99%

“…In the present study an attempt has been undertaken to compare the homocysteine level in the blood of women with reproductive disorders with the genotype for the most significant SNP of the folic acid cycle genes network. Previously in this field the advantage of simultaneous analysis of several polymorphisms of the folic acid cycle genes was demonstrated [1,2]. As a result of the analysis of the available data, four polymorphisms were selected for further analysis: 667 C>T (rs1801133) and 1298 A>C (rs1801131) of the MTHFR gene, 2756…”

Section: Introductionmentioning

confidence: 99%

The Fluctuations in Homocysteine Level Caused by Various Combinations of Folic Acid Cycle Genes Snp Alleles as a Factor in the Course of Pregnancy Violation

Ev¹,

Yn²,

Ma³

et al. 2018

Adv Tech Biol Med

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The presence of pathological alleles of single nucleotide polymorphisms (SNP) of the folic acid cycle genes is one of the female reproductive system violation factors including habitual miscarriage and pre-eclampsia. The realizing mechanism for this genetic predisposition is hyperhomocysteinemia-homocysteine level increasing in the blood. This study presenting an attempt to find the relationship between the genotype for the four SNPs of the three folate cycle genes-C677T and A1298C of the MTHFR gene, A2756G of the MTR gene and the A66G of the MTRR gene and the homocysteine level in the blood of women with impaired pregnancy. As a result no direct correlation was found but it was found a statistically significant interlation between the presence of pathological alleles of the studied SNP and the mean square deviation (σ) of the homocysteine level fluctuations over time. For the polymorphism C677T of the MTHFR gene σ of the homocysteine blood level fluctuation is increased up to four times in women with a homozygous pathological state TT compared with the normal homozygotes CC. The clinical importance of monitoring the homocysteine blood level has been shown especially for women with folate cycle genes pathological alleles' presence.

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The effect of single nucleotide genetic polymorphisms of folic acid cycle on the female reproductive system disorders

Cited by 4 publications

References 10 publications

Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation

Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation

Toward optimal set of single nucleotide polymorphism investigation before IVF

The Fluctuations in Homocysteine Level Caused by Various Combinations of Folic Acid Cycle Genes Snp Alleles as a Factor in the Course of Pregnancy Violation

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