Русский
Pharmacogenetic approaches to optimization of micronutrient support regimens in the period of pregravid preparation
DOI: https://dx.doi.org/10.18565/pharmateca.2022.9.38-45
E.V. Shikh, A.V. Putintseva
I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
Background. Support for women’s reproductive health is one of the most important directions in the development of healthcare in Russia, since the health of the younger generation depends on the health of expectant mothers.
Objective. Optimization of pregravid preparation by using various micronutrient support regimens, taking into account the pharmacogenetic characteristics of patients.
Methods. The observational study was carried out in the outpatient settings with participation of 194 women aged 20 to 38 years who applied for pregravid preparation. Depending on the corrective micronutrient support, patients were divided into 2 groups: group 1 received 451 µg metafolin with 2.6 µg cyanocobalamin; Group 2 received 400 µg folic acid. Genotyping of polymorphic loci MTHFR-677C>T, MTHFR-1298A>C, MTR-2756A>G, MTRR-66A>G was carried out by polymerase chain reaction. Quantitative analysis of the folate levels was performed by the chemiluminescence immunoassay. Against the background of micronutrient support for 3 months, the dynamics of the blood plasma folate was assessed. Descriptive statistics and analytical methods were used for analysis. Descriptive statistics of continuous quantitative data are presented as mean (M) and arithmetic mean error (±m). Statistical significance of differences was assessed using Student’s parametric test. Pearson’s χ2 test was used to assess the correspondence of genotype distributions and to compare the distributions of genotype frequencies in the samples. For non-normal distributions, group analysis was performed using the nonparametric Wilcoxon test and the Mann-Whitney test. Values were considered statistically significant at p≤0.05. Statistical analysis was carried out using the IBM SPSS Statistics 23.0 package. To calculate Pearson’s χ2, the Rstudio development environment version 1.0.143 for the R programming language was used.
Results. It was found that both regimens were effective in women with normal genotypes: MTHFR-677CC, MTHFR-1298AA, MTR-2756AA, MTRR-66AA, in which there is no carriage of a rare allele and in women with a heterozygous variant of carriage of a rare allele with MTHFR-677CT, MTHFR -1298AC, MTR-2756AG, MTRR-66AG genotypes. In women with a homozygous carrier variant of a rare allele with MTHFR-677TT, MTHFR-1298CC, MTR-2756GG, MTRR-66GG genotypes, only the use of 451 µg metafolin with 2.6 µg cyano-cobalamin provided effective micronutrient support.
Conclusion. At the stage of pregravid preparation, genetic screening is advisable to identify rare alleles of polymorphisms of the genes of the main enzymes of the folate cycle. This provides a personalized approach to the micronutrient support regimen and optimal correction in order to effectively prevent congenital malformations and other complications of pregnancy.
Objective. Optimization of pregravid preparation by using various micronutrient support regimens, taking into account the pharmacogenetic characteristics of patients.
Methods. The observational study was carried out in the outpatient settings with participation of 194 women aged 20 to 38 years who applied for pregravid preparation. Depending on the corrective micronutrient support, patients were divided into 2 groups: group 1 received 451 µg metafolin with 2.6 µg cyanocobalamin; Group 2 received 400 µg folic acid. Genotyping of polymorphic loci MTHFR-677C>T, MTHFR-1298A>C, MTR-2756A>G, MTRR-66A>G was carried out by polymerase chain reaction. Quantitative analysis of the folate levels was performed by the chemiluminescence immunoassay. Against the background of micronutrient support for 3 months, the dynamics of the blood plasma folate was assessed. Descriptive statistics and analytical methods were used for analysis. Descriptive statistics of continuous quantitative data are presented as mean (M) and arithmetic mean error (±m). Statistical significance of differences was assessed using Student’s parametric test. Pearson’s χ2 test was used to assess the correspondence of genotype distributions and to compare the distributions of genotype frequencies in the samples. For non-normal distributions, group analysis was performed using the nonparametric Wilcoxon test and the Mann-Whitney test. Values were considered statistically significant at p≤0.05. Statistical analysis was carried out using the IBM SPSS Statistics 23.0 package. To calculate Pearson’s χ2, the Rstudio development environment version 1.0.143 for the R programming language was used.
Results. It was found that both regimens were effective in women with normal genotypes: MTHFR-677CC, MTHFR-1298AA, MTR-2756AA, MTRR-66AA, in which there is no carriage of a rare allele and in women with a heterozygous variant of carriage of a rare allele with MTHFR-677CT, MTHFR -1298AC, MTR-2756AG, MTRR-66AG genotypes. In women with a homozygous carrier variant of a rare allele with MTHFR-677TT, MTHFR-1298CC, MTR-2756GG, MTRR-66GG genotypes, only the use of 451 µg metafolin with 2.6 µg cyano-cobalamin provided effective micronutrient support.
Conclusion. At the stage of pregravid preparation, genetic screening is advisable to identify rare alleles of polymorphisms of the genes of the main enzymes of the folate cycle. This provides a personalized approach to the micronutrient support regimen and optimal correction in order to effectively prevent congenital malformations and other complications of pregnancy.
About the Autors
Corresponding author: Evgenia V. Shikh, Dr. Sci. (Med.), Professor, Head of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, N.V. Sklifosovsky Institute of Clinical Medicine, Sechenov University, Moscow, Russia; shikh_e_v@staff.sechenov.ru
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