Medical and Social Justification of the Implementation of the Optimized Model of Prevention of Genetically Determined Reproductive Losses

Among the objects of organizational influence of the health care system on reproductive losses, miscarriages and congenital malformations (birth defects) are the most important. Diagnosis of most genetic, chromosomal diseases and malformations of the embryo and fetus is performed using biochemical, cytogenetic, molecular genetic tests and ultrasound diagnostic. Many clinical geneticists focus on birth defects and miscarriages associated with folate cycle disorders related with the greatest number of reproductive losses. We studied levels of homocysteine, folic acid and vitamin B12 in pregnant blood and polymorphic genes C677T MTHFR and A66G MTRR considered due to folate cycle disorders. The purpose of the study was to analyze the organizational aspects of the existing model for the prevention of genetically determined reproductive losses and to propose measures to improve the model. Material and methods. The methods of system approach and analysis, bibliosemantic, prospective, economic, expert assessments provided by the specialty passport (14.02.2003) "Social Medicine" were used for the research. Research period: 2008–2018. Place of research: "Interregional Specialized Medical and Genetic Center – Center for Rare (Orphan) Diseases" of Kharkiv Regional Council. Genetic maps of the archive and own patients, normative-legal acts, data of medical statistics were analyzed. Results and discussion. The study suggested an optimized model for the prevention of genetically determined reproductive losses, which took into account examinations for homocysteine, folic acid, vitamin B12 levels, MTHFR and MTRR genes to find their polymorphism, ultrasound, prevention using diet and vitamin therapy, involving gynecologists, family physicians and clinical geneticists. The principles of accessibility, safety, effectiveness, timeliness, cost-effectiveness, protection of rights and freedoms (non-discrimination), personal orientation, legal basis, cooperation with other medical and non-medical organizations and institutions, prevention character, complexity and variety of forms of physician’s cooperation who provide care to pregnant with reproductive losses in anamnesis, couples planning a pregnancy, newborns with birth defects, chromosomal, genetic diseases and syndromes. The efficient and uninterrupted operation of the developed optimized system is ensured with the participation of "feedback" mechanisms. Adherence to the proposed model will provide an opportunity to significantly reduce reproductive losses in the coming years in Ukraine, provided that its principles are included in the relevant national programs and protocols

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THE STUDY OF SOCIAL-MEDICAL AND GENETIC RISKS OF REPRODUCTIVE LOSSES

ScienceRise ◽

10.21303/2313-8416.2021.001668 ◽

2021 ◽

pp. 41-49

Author(s):

Tarana Dzhafar Kyzy Alieva

Keyword(s):

Folic Acid ◽

Methylenetetrahydrofolate Reductase ◽

Medical Genetic ◽

Methionine Synthase Reductase ◽

Reproductive Losses ◽

Genes Encoding ◽

Depth Study ◽

Genetically Determined ◽

Folate Cycle ◽

Technological Product

Object of research: homozygous and heterozygous disorders of genes encoding the enzymes of the folate cycle, methylenetetrahydrofolate reductase (MTHFR) and methionine-synthase-reductase (MTRR). Solved problem: an in-depth study of genetically determined risk factor’s influence for reproductive losses associated with homozygous and heterozygous disorders of folate cycle genes. Main scientific results: in-depth study of genetically determined reproductive losses as a systemic phenomenon was held. The structural characteristics of reproductive losses in population and significant predominance of pathology in the pedigrees of those examined with a burdened obstetric history of reproductive losses were determined. Also, a significant increase in the chances of reproductive loss in patients with heterozygous and homozygous inheritance of MTHFR and MTRR genes was determined. A correlation effect on the degree of genomic polymorphism of the MTHFR and MTRR gene was noted. Area of practical use of research results: medical-genetic institutions. Innovative technological product: determination of genetically risk factors for growth of reproductive losses of the population associated with homozygous and heterozygous disorders of genes encoding the enzymes of the folate cycle (MTHFR C677T and MTRR A66G). Timely adjustment of folic acid levels allows to prevent birth defects and reduce reproductive losses Scope of application of the innovative technological product: clinical medical-genetic practice using the ability to determine the polymorphism of genes MTHFR and MTRR, which makes it possible to timely adjust the level of folic acid and prevent the reproductive losses.

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Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006949117 ◽

2020 ◽

Vol 117 (27) ◽

pp. 15837-15845 ◽

Cited By ~ 7

Author(s):

Daniel J. Kim ◽

Arvind Venkataraman ◽

Priyanka Caroline Jain ◽

Eleanor P. Wiesler ◽

Melody DeBlasio ◽

...

Keyword(s):

Folic Acid ◽

Vitamin B12 ◽

Aryl Hydrocarbon Receptor ◽

Birth Defects ◽

Target Genes ◽

De Novo ◽

Human Cancer ◽

Erythroid Progenitors ◽

Aryl Hydrocarbon ◽

Significant Difference

Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.

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SONOGRAPHIC MARKERS OF ASSOCIATION OF FOLATE CYCLE POLYMORPHIC GENES AND EPIGENETIC FACTORS

International Medical Journal ◽

10.37436/2308-5274-2021-1-17 ◽

2021 ◽

pp. 92-100

Author(s):

T. D. Alieva

Keyword(s):

Pregnant Women ◽

Genetic Diseases ◽

Molecular Genetic ◽

Epigenetic Factors ◽

Childbearing Age ◽

Screening Programs ◽

Reproductive Losses ◽

Adverse Pregnancy ◽

Genetically Determined ◽

Folate Cycle

Reproductive losses in Ukraine are about twice the European average, but have the same causes: miscarriage, abortion, malformations, parental infertility, death of women of childbearing age and children under six days of age. The study focuses on genetically determined reproductive losses associated with folate cycle polymorphism, some other polymorphisms, and epigenetic factors that increase the risk of adverse pregnancy outcomes. Methods of systematic and demographic analysis studied the indices of medical and statistical observation of the population of the Kharkiv region within the period of 2008−2018 with an emphasis on the results of biochemical, molecular genetic and sonographic examinations of pregnant women. Data on the number of examined pregnant women were analyzed using ultrasonographic and biochemical studies at the level of alpha−fetoprotein, chorionic gonadotropin and free estriol in the framework of selective screening programs for pregnant women. Statistical data on the number of fetuses and newborns who died during the first − sixth day after birth, with a distribution on the basis of full−term have been studied. The data are compared with similar national indices. The directions of reducing the reproductive losses are offered, including complex inspection of pregnant women with use of ultrasonography, biochemical and molecular−genetic methods of diagnostics of genetic diseases and defects of fetus development. Among the epigenetic factors we have identified obesity and old age of pregnant women, among the types of abortions we did medical abortions associated with stillborn pregnancies, as well as miscarriages. The findings of the study can be used to minimize the effects of risk factors for reproductive loss in the activity of general practitioners. Key words: polymorphism of folate cycle genes, reproductive losses, miscarriage, congenital malformations of fetus, ultrasonography.

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Features of folate cycle disorders in children with ASD

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v19i4.46634 ◽

2020 ◽

Vol 19 (4) ◽

pp. 737-742

Author(s):

DmitryV Maltsev

Keyword(s):

Medical Science ◽

Autism Spectrum ◽

Control Group ◽

Children With Asd ◽

Spectrum Disorders ◽

Immunological Research ◽

Cycle Disorders ◽

Genetically Determined ◽

Folate Cycle

Aim: to show the effect of genetically determined folate cycle deficiency in children with autism spectrum disorders (ASD). Participants: 89 children (57 boys; 32 girls, Ukraine, 2-10 years old); participants were diagnosed with ASD. The control group consisted of 34 children with ASD. Diagnostic methods:polymerase chain reaction (PCR), complex immunological research, diagnosis of infection, determination of biomarkers. Results and discussion:Hyperhomocysteinemia was revealed in 87% of cases (p <0.05; Z <Z0.05).The indicated form of immunodeficiency was noted among 91% participants in the study, while only in 27% children of the control group had a similar immunological phenotype.The serum concentration of folic acid was increased in 64%, and reduced in 21% of cases. An increase of vitamin B12 also occurred in 64%, and vitamin B6 - only in 43% of cases. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.737-742

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