The role of MTHFR, MTRR, MTR1 intergenic interaction in the development of folate metabolism disturbance in patients with reproductive disorders

Gorovenko N.G.; Kyriachenko S.P.; Rossokha Z.I.

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3(2) (125) – V/VI 2018 :

Original research

The role of MTHFR, MTRR, MTR1 intergenic interaction in the development of folate metabolism disturbance in patients with reproductive disorders

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Gorovenko N.G.¹, Kyriachenko S.P.², Rossokha Z.I.³

¹National Medical Academy of Postgraduate Education named after P.L. Shupik, Kyiv
²SI «Reference center for molecular diagnostics of the Ministry of Health of Ukraine», Kyiv
³Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv

Summary. Purpose. Role determination of MTHFR, MTRR, MTR1 intergenic interaction in the development of folate metabolism disturbance in patients with reproductive disorders. Object and methods. Molecular genetic studies of genes: MTHFR (C677T, rs1801133, A1298C, rs1801131), MTRR (A66G, rs1801394), MTR1 (A2756G, rs1805087) and biochemical indicators of folate metabolism in 185 patients with reproductive disorders were performed. Results. Hyperhomocysteinemia (autosomal recessive hereditary metabolic disease) associated with mutations in folate metabolism genes were found in 20% of women with reproductive disorders. The level of homocysteine was significantly increased in patients with the 677TT genotype in the MTHFR gene and its combinations with 1298AA, 66AA, 66GG and 2756GG genotypes of the MTHFR, MTRR and MTR1 genes, while the levels of folic acid and vitamin B12 were decreased. A significant model risk of hyperhomocysteinemia was four-locus, involving the MTHFR, MTRR, MTR1 genes. The risk of hyperhomocysteinemia development was increased significantly with genotypes combinations: 677TT/1298AA/66GG, 1298AC/2756AG/66AG, and decreased with combination 677CC/1298AC/2756AA. The differences in folate metabolism indices are required further analysis of gene — factor interactions, taking into account vitamin and nutrient consumption.

DOI 10.32471/umj.1680-3051.125.126970

Z.I. Rossokha, S.P. Kiryachenko, N.G. Gorovenko

Key words: genetic polymorphism, hyperhomocysteinemia, reproductive disorders.

Published: 05.07.2018

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