DOI: https://doi.org/10.18370/2309-4117.2020.52.67-72

Pathogenetic substantiation of personified correction of folate cycle disorders using a complex with metapholine for the congenital malformations prevention

І. В. Руденко, В. П. Міщенко

Abstract


Congenital malformations are pathology with a multifactorial etiology. Among their many endogenous, exogenous factors and hereditary predisposition are important. In particular a decrease in follicular enzymes (MTHFR, MTR, MTRR) activity at the genetic level, as well as a deficiency of vitamins and vitamin-like compounds of group B.

Objective: to provide a pathogenetic justification for personified correction of disorders in the folate cycle in biological parents preparing for pregnancy to prevent congenital malformations in their children by using folates containing metafolin (5-MTHF).

Materials and methods. The study involved 75 women and 75 men (biological parents) who had children/fetuses with congenital malformations in previous pregnancies, and 75 newborn children of these couples. All of them used the proposed preconceptional preparation. Alleles of folate cycle enzyme genes (MTHFR, MTR, MTRR) were determined by polymerase chain reaction in blood and saliva.

Results. A high frequency of polymorphism of the folate cycle enzyme genes was observed in men among subjects (father, mother, child). The indicator was 77.7% compared with 68.7% in mothers and 60.7% in their children. The frequency of homozygous alleles was highest in parents (men) – 19.6%, lower in mothers – 13.1% and in children – 12.7%. Result of heterozygous alleles decreased from children indicator (87.3%) to their mothers (86.7%) and parents (80.4%).

Conclusions. Obtained results emphasize the practical importance for determining the alleles of the folate cycle enzyme genes (MTHFR, MTR, MTRR) at the stage of preconception preparation for pregnancy in biological parents and then in their newborn children from the standpoint of preventive medicine. Reduced activity of the corresponding enzymes pathogenetically explains the feasibility of using folate complexes containing active folate metafolin (5-MTHF) in order to prevent congenital malformations.


Keywords


pathogenetic substantiation; patient specific correction; folate cycle; metafolin; 5-MTHF; congenital malformations

References


Baranov, V.S. Genetic passport – the basis of individual and predictive medicine. St. Petersburg. Publishing House N–L (2009): 528 p.

Kuliutsina, E.R., Tatarchenko, I.P., Levashova, O.A., et al. “The relationship of homocysteine and genetic polymorphisms causing folate metabolism disorders in a healthy population.” Klinicheskaya Laboratornaya Diagnostika 2 (2017): 82–7.

Kovalev, V.V., Potapov, N.N. “Molecular genetic factors of an undeveloped pregnancy with an unknown etiology.” Ural Medical Journal 2 (2016): 35–9.

Radzinskiy, V.E., Ryabinkina, T.S., Bril, Y.A., et al. Pregnancy ration correction: evidence data (newsletter). Moscow. Status Praesens (2018): 28 p.

Liskovskyi, S.V. Clinical and laboratory evaluation of gestational periods in women with cyanocobalamin deficiency. Thesis abstract for PhD degree, specialty 14.01.01 “Obstetrics and Gynecology”. Odesa (2013): 20 p.

Medvedev, D.V., Zvyagina, V.I. “Molecular mechanisms of the toxic effect of homocysteine.” Kardiologicheskij Vestnik 1 (2017): 52–7.

Mishchenko, V.P. Placental insufficiency in the current ecological situation (diagnosis, prevention and treatment). Thesis abstract for MD degree, specialty 14.01.01 “Obstetrics and Gynecology”. Odesa (1998): 32 p.

Logutova, L.S., Budykina, T.S., Melnikov, A.P., et al. “Optimization of pregravid preparation in patients with a history of obstetric loss.” Rossiyskiy vestnik akushera-ginekologa 2 (2017): 74–7.

Mishchenko, V.P., Rudenko, I.V., Zaporozhchenko, M.B., et al. “Peculiarities of pregravid preparation of women of different nationalities.” Actual Problems of Pediatry, Obstetrics and Gynecology 1.19 (2017): 105–10.

Kerkeshko, G.O., Dorofeykov, V.V., Patrukhina N.A., et al. “The role of active vitamin B12 (holotranscobalamin) in the formation of anemia in pregnant women.” Journal of Obstetrics and Women's Diseases 5 (2015): 96–105.

Rudenko, I.V. “Analysis of medical records of parents whom children were born with birth defects.” Odesa Medical Journal 112.2 (2009): 59–62.

Rudenko, I.V. “Congenital malformations of the musculoskeletal system in newborns.” PAG 71.2 (2009): 26–8.

Rudenko, I.V. Prediction and prevention of birth defects in children in modern environmental conditions. Thesis abstract for MD degree, specialty 14.01.01 “Obstetrics and Gynecology”. Odesa (2010): 43 p.

Engel, S.M., Olshan, A.R., Siega-Riz, A.M. “Polymorphisms in folate metabolizing genes and risk for spontaneous preterm and small-for-gestational age birth.” Am J Obstet Gynecol 195.5 (2006): 1231.

Metayer, C., Milne, E., Dockerty, I.D., et al. “Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring.” Epidemiology 25 (2014): 811–22.

Clement, A., Clement, P., Menezo, Y., et al. “MTHFR in a large infertile cohort of more than 2500 patients: incidence, effect of treatment and impact on other systems.” Abstracts of 27th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) In Partnership with RBMO. Paris (2019).

Clement, P., Menezo, Y., Alvarez, S., et al. “Treatment for MTHFR (methylenetetrahydrofolate reductase) C677T mutations carries with 5 methylenetetrahydrofolate (5 MTHFR) improves their art outcomes.” Abstracts of 27th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) In Partnership with RBMO. Paris (2019).

Zaichenko, A.V. “Folates and omega-3-PUFAs in obstetrics: more than the prevention of neural tube defects.” Health of Ukraine. Gynecology. Obstetrics. Reproductology 1 (2018): 1–4.

Kurmacheva, N.A., et al. “Pregnancy and polymorphisms of the folate cycle genes: what dose and form of folate to choose?” Doctor.ru. Gynecology. Endocrinology 14.115 (2015): 49–54.

Czeizel, A.E., Dudas, I., Vereczkey, A., et al. “Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.” Heart Defects Nutrients 5.11 (2013): 4760–75.


GOST Style Citations


1.            Баранов, В.С. Генетический паспорт – основа индивидуальной и предиктивной медицины / В. С. Баранов. – СПб.: Изд-во Н–Л, 2009. – 528 с.

2.            Кулюцина, Е.Р. Взаимосвязь показателей гомоцистеина и генетических полиморфизмов, обуславливающих нарушения обмена фолатов, у здорового населения / Е.Р. Кулюцина, И.П. Татарченко, О.А. Левашова и др. // Клиническая лабораторная диагностика. – 2017. – № 2. – С. 82–87.

3.            Ковалев, В.В. Молекулярно-генетические факторы неразвивающейся беременности с неустановленной этиологией / В.В. Ковалев, Н.Н. Потапов // Уральский медицинский журнал. – 2016. – № 2. – С. 35–39.

4.            Радзинский, В.Е. Коррекция рациона беременных: доказательные данные (информационный бюллетень) / В.Е. Радзинский, Т.С. Рябинкина, Ю.А. Бриль и др. – М.: Status Prаesens, 2018. – 28 c.

5.            Лісковський, С.В. Клініко-лабораторна оцінка гестаційних періодів у жінок із дефіцитом ціанокобаламіну : автореф. дис. … к. мед. н. : спец. 14.01.01 «Акушерство і гінекологія» / С.В. Лісковський. – Одеса, 2013. – 20 с.

6.            Медведев, Д.В. Молекулярные механизмы токсического действия гомоцистеина / Д.В. Медведев, В.И. Звягина // Кардиологический вестник. – 2017. – № 1. – С. 52–57.

7.            Міщенко, В.П. Плацентарна недостатність в умовах сучасної екологічної ситуації (діагностика, профілактика та лікування) : автореф. дис. … д. мед. н. : спец. 14.01.01 «Акушерство і гінекологія» / В.П. Міщенко. – Одеса, 1998. – 32 с.

8.            Логутова, Л.С. Оптимизация прегравидарной подготовки у пациенток с акушерскими потерями в анамнезе / Л.С. Логутова, Т.С. Будыкина, А.П. Мельников и др. // Российский вестник акушера-гинеколога. – 2017. – № 2. – С. 74–77.

9.            Міщенко, В.П. Особливості прегравідарної підготовки жінок різних національностей / В.П. Міщенко, І.В. Руденко, М.Б. Запорожченко та ін. // Актуальні питання педіатрії, акушерства та гінекології. – 2017. – № 1 (19). – С. 105–110.

10.          Керкешко, Г.О. Роль активного витамина В12 (холотранскобаламина) в формировании анемии беременных / Г.O. Керкешко, В.В. Дорофейков, Н.А. Патрухина и др. // Журнал акушерства и женских болезней. – 2015. – № 5. – С. 96–105.

11.          Руденко, І.В. Аналіз медичної документації батьків, у яких діти народилися з природженими вадами розвитку / І.В. Руденко // Одеський медичний журнал. – 2009. – Т. 112, № 2. – С. 59–62.

12.          Руденко, І.В. Природжені вади розвитку опорно-рухової системи у новонароджених / І. В. Руденко // ПАГ. – 2009. – Т. 71, № 2. – С. 26–28.

13.          Руденко, І.В. Прогнозування та профілактика природжених вад розвитку в дітей у сучасних екологічних умовах : автореф. дис. … д. мед. н. : спец. 14.01.01 «Акушерство і гінекологія» / І. В. Руденко. – Одеса, 2010. – 43 с.

14.          Engel, S.M., Olshan, A.R., Siega-Riz, A.M. “Polymorphisms in folate metabolizing genes and risk for spontaneous preterm and small-for-gestational age birth.” Am J Obstet Gynecol 195.5 (2006): 1231.

15.          Metayer, C., Milne, E., Dockerty, I.D., et al. “Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring.” Epidemiology 25 (2014): 811–22.

16.          Clement, A., Clement, P., Menezo, Y., et al. “MTHFR in a large infertile cohort of more than 2500 patients: incidence, effect of treatment and impact on other systems.” Abstracts of 27th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) In Partnership with RBMO. Paris (2019).

17.          Clement, P., Menezo, Y., Alvarez, S., et al. “Treatment for MTHFR (methylenetetrahydrofolate reductase) C677T mutations carries with 5 methylenetetrahydrofolate (5 MTHFR) improves their art outcomes.” Abstracts of 27th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) In Partnership with RBMO. Paris (2019).

18.          Зайченко, А.В. Фолаты и омега-3-ПНЖК в акушерстве: больше чем профилактика дефектов нервной трубки / А.В. Зайченко // Здоров’я України. Гінекологія. Акушерство. Репродуктологія. – 2018. – № 1. – С. 1–4.

19.          Курмачева, Н.А. Беременность и полиморфизмы генов фолатного цикла: какую дозу и форму фолатов выбрать? / Н.А. Курмачева и др. // Доктор.ру. Гинекология. Эндокринология. – 2015. – № 14 (115). – С. 49–54.

20.          Czeizel, A.E., Dudas, I., Vereczkey, A., et al. “Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.” Heart Defects Nutrients 5.11 (2013): 4760–75.





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