Polymorphic substitutions in folate cycle genes as predictors of hyperhomocysteinemia in children

Introduction. Mutant alleles of genes of folate cycle enzymes can lead to the significant deterioration of its function and varying severity of pathology. Several defects in these genes lead to severe hyperhomocysteinemia, the most common form of which is a deficiency of cystathionine beta-synthase B.

Aim: to establish polymorphic substitutions in the genes of folate cycle enzymes that contribute to the formation of hyperhomocysteinemia in children.

Materials and methods. Two hundred seventy one children aged of 13–18 years were examined. The analysis of genetic polymorphisms of the folate cycle was carried out using a molecular genetic method. Quantitative determination of the blood homocysteine and folic acid level was performed by chemiluminescent immunoassay on microparticles. Statistical data processing was carried out using Statistica 6.1 application programs (StatSoft Inc., USA).

Results. The frequency of the T allele of the MTHFR 677 gene was revealed to be higher in adolescents of the main group compared with the control (p = 0.043). The frequency of the homozygous genotype 66 AA of the MTRR gene in children of the comparison group was significantly higher (p = 0.049), however, the heterozygous genotype 66 AG of the MTRR gene was significantly more often detected in adolescents of the main group (p = 0.008). The average concentrations of homocysteine in children of the main group were 11.6 mmol/L, in adolescents of the control group 9.3 mmol/L (p = 0.021). Hyperhomocysteinemia in children of the main group was detected in 217 (80.1%) adolescents, and in 57 (49.6%) children of the control group (p < 0.001). The baseline serum folate level was determined in the children of the main group. The average amount of vitamin B9 in the blood of children of the main group was 3.7 ng/ml, and in 145 (53.5%) children this indicator was significantly reduced.

Conclusion. Low levels of folic acid contribute to an increase in homocysteine in blood plasma. Taking vitamin B9 and vitamin folate complexes significantly reduces the level of homocysteine in blood plasma (p < 0.001).

Contribution:
Strozenko L.A. — concept, research design;
Ponomarev V.S., Sanina O.O. Sukmanova I.A., Shevchenko K.I. — collection and processing of material;
Lobanov Yu.F., Skudarnov E.V. — editing the text;
Dorokhov N.A. — writing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. This work was carried out within the framework of a grant from the Governor of the Altai Territory in the field of medical prevention, rehabilitation and health protection of the population.

Conflict of interest. The authors declare no conflict of interest.

Received: January 11, 2024
Accepted: January 30, 2024
Published: February 28, 2024

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