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Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis

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Abstract

The contents of homocysteine (HCy), cyanocobalamin (vitamin B12), folic acid (vitamin B9), and pyridoxine (vitamin B6) were analyzed and the genotypes of the main gene polymorphisms associated with folate metabolism (C677T and A1298C of the MTHFR gene, A2756G of the MTR gene and A66G of the MTRR gene) were determined in children at the onset of multiple sclerosis (MS) (with disease duration of no more than six months), healthy children under 18 years (control group), healthy adults without neurological pathology, adult patients with MS at the onset of disease, and adult patients with long-term MS. A significant increase in the HCy levels was found in children at the MS onset compared to healthy children of the corresponding age. It was established that the content of HCy in children has a high predictive value. At the same time, an increase in the HCy levels was not accompanied by the deficiency of vitamins B6, B9, and B12 in the blood. The lack of correlation between the laboratory signs of vitamin deficiency and HCy levels may be due to the polymorphic variants of folate cycle genes. An increased HCy level should be considered as a marker of functional disorders of folate metabolism accompanying the development of pathological process in pediatric MS. Our finding can be used to develop new approaches to the prevention of demyelination in children and treatment of pediatric MS.

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Fig. 1.
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Abbreviations

CNS:

central nervous system

Hcy:

homocysteine

MS:

multiple sclerosis

MTHF:

methylenetetrahydrofolate reductase

MTR:

methionine synthase

MTRR:

methionine synthase reductase

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Funding

The work was carried out with financial support from the Russian Science Foundation and the St. Petersburg Science Foundation (project no. 22-25-20191).

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Authors and Affiliations

  1. Institute of Experimental Medicine, 197022, Saint Petersburg, Russia

    Victoria I. Lioudyno, Evgenia A. Tsymbalova, Ekaterina A. Chernyavskaya, Alexander V. Dmitriev & Irina N. Abdurasulova

  2. Pediatric Research and Clinical Centre for Infectious Diseases, 197022, Saint Petersburg, Russia

    Elena Y. Scripchenko

  3. Almazov National Medical Research Center, 197341, Saint Petersburg, Russia

    Gennadij N. Bisaga

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  1. Victoria I. Lioudyno
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  2. Evgenia A. Tsymbalova
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Contributions

V.I.L. wrote the text of the article; E.A.Ts. and E.A.Ch. conducted the experiments; V.I.L., G.N.B., E.Yu.S., A.V.D., and I.N.A. discussed the results; E.Yu.S. edited the manuscript; A.V.D. developed the concept; A.V.D. and I.N.A. supervised the study.

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Correspondence to Victoria I. Lioudyno.

Ethics declarations

All procedures performed during the study were in accordance with the ethical standards of the national research ethics committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed voluntary consent was obtained from all patients and control subjects included in the study. The study was approved by the Local Ethics Committee of the Federal State Budgetary Institution “IEM” protocol no. 2/22 dated 04/06/2022. The authors of this work declare that they have no conflicts of interest.

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Lioudyno, V.I., Tsymbalova, E.A., Chernyavskaya, E.A. et al. Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis. Biochemistry Moscow 89, 562–573 (2024). https://doi.org/10.1134/S0006297924030143

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