Polymorphism of folate cycle genes as a risk factor of hyperhomocysteinemia

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A.M. Ivanov1, A.Zh. Gil'manov2, N.N. Malyutina3, Ya.B. Khovaeva3, O.Yu. Nenasheva3,4, G.I. El'kin1, D.Yu. Sosnin3


1Military Medical Academy named after S.M. Kirov, 6 Akademika Lebedeva Str., Saint Petersburg, 194044, Russian Federation
2Bashkirian State Medical University, 3 Lenina Str., Ufa, 450000, Russian Federation
3Perm State Medical University named after Academician E.A. Wagner, 26 Petropavlovskaya Str., Perm, 614000, Russian Federation
4«MedLabEkspress» LLC, 14 A Gaidara Str., Perm, 614000, Russian Federation


Hyperhomocysteinemia (HHc) is a new factor being considered at the moment that can cause damage to vessel walls. Its occurrence depends on genetic peculiarities of a body.
Our research goal was to estimate frequency of genetic polymorphisms (SNP) in folate cycle genes among people living in Perm region and its influence on homocysteine (Hc) concentration in blood serum.
We examined 189 women (32.2±5.25). Hc concentration in blood serum was determined with immune chemiluminescent procedure. We examined frequency of SNP in folate cycle genes with pyrosequencing.
Homozygote state as per minor alleles in methylene tetrahydrofolate reductase (MTHFR) gene (rs 1801133 и rs 1801131) and MTR gene (rs 1805087) was registered 7.5, 5.4, and 13.75 times less frequently than homozygote state as per neutral alleles. Heterozygote state prevailed for genes of methionine synthase reductase and folate transport protein among examined SNP. Homozygotes as per minor allele SNP in MTHFR gene (Ala222Val; rs 1801133) had higher Hc concentration in blood serum that amounted to 8.476 ± 3.193 mmol/L and was 1.276 times higher than the same parameter in homozygotes as per neutral allele (р=0.0036). We didn’t establish any influence on Hc contents in blood serum for the remaining 4 SNP in folate cycle genes (р> 0.1).
Examined SNP in MTHFR and MTR genes tended to have neutral alleles more frequently than minor ones. SNP in genes of other examined proteins belonging to folate cycle didn’t have any differences in frequency of examined alleles. We didn’t detect a combination of homozygote state as per two SNP in MTHFR gene or homozygote state as per one SNP and heterozygote state as per another one in a genome. Only SNP in MTHFR gene (Ala222Val, rs 1801133) authentically causes increase in homocysteine concentration out of all the examined SNP in genes of folate cycle enzymes and proteins.

homocysteine, hyperhomocysteinemia, single-nucleotide polymorphisms, folate cycle genes, methylene tetrahydrofolate reductase, methionine synthase, methionine synthase reductase, folate transport protein
Ivanov A.M., Gil'manov A.Zh., Malyutina N.N., Khovaeva Ya.B., Nenasheva O.Yu., El'kin G.I., Sosnin D.Yu. Genetic polymorphism of folate cycle genes as a risk factor of hyperhomocysteinemia. Health Risk Analysis, 2020, no. 4, pp. 137–146. DOI: 10.21668/health.risk/2020.4.16.eng
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