Polymorphism of folate cycle genes as a risk factor of hyperhomocysteinemia

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.

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Methionine Synthase Reductase 66A→G Polymorphism Is Associated with Increased Plasma Homocysteine Concentration When Combined with the Homozygous Methylenetetrahydrofolate Reductase 677C→T Variant

Journal of Nutrition ◽

10.1093/jn/134.11.2985 ◽

2004 ◽

Vol 134 (11) ◽

pp. 2985-2990 ◽

Cited By ~ 47

Author(s):

Jaimie D. Vaughn ◽

Lynn B. Bailey ◽

Karla P. Shelnutt ◽

Kristina M. von-Castel Dunwoody ◽

David R. Maneval ◽

...

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Plasma Homocysteine ◽

Methionine Synthase ◽

Homocysteine Concentration ◽

Methionine Synthase Reductase ◽

Plasma Homocysteine Concentration

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Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

Science Advances ◽

10.1126/sciadv.1501678 ◽

2016 ◽

Vol 2 (6) ◽

pp. e1501678 ◽

Cited By ~ 53

Author(s):

Till F. M. Andlauer ◽

Dorothea Buck ◽

Gisela Antony ◽

Antonios Bayas ◽

Lukas Bechmann ◽

...

Keyword(s):

Multiple Sclerosis ◽

Genome Wide Association Study ◽

Immune Cell ◽

Susceptibility Loci ◽

Genome Wide ◽

A Genome ◽

Genetic Substructure ◽

Epigenetic Signatures ◽

Folate Cycle ◽

Ms Pathogenesis

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genesL3MBTL3,MAZ,ERG, andSHMT1. The lead variant atSHMT1was replicated in an independent Sardinian cohort. Products of the genesL3MBTL3,MAZ, andERGplay important roles in immune cell regulation.SHMT1encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

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Breast cancer prevention in districts affected by the Chernobyl nuclear power plant accident beginning from child ages

Environment & Health ◽

10.32402/dovkil2021.01.029 ◽

2021 ◽

pp. 29-35

Author(s):

Yu.I. Bandazhevskyi ◽

◽

N.F. Dubovaya ◽

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Genetic Predisposition ◽

Nuclear Power ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

The Body ◽

Exclusion Zone ◽

Folate Cycle

The aim of this paper was to assess the prevalence of the T risk allele of the MTHFR:677 genetic polymorphism in a group of girls from Ivankovsky and Polessky districts located near the Chernobyl exclusion zone. In addition, we assessed variants of combined carriership of the T allele with risk alleles of other genetic polymorphisms regulating the folate cycle. Research methods. Immunochemical, statistical. Results. Genetic predisposition to breast cancer risk was analyzed in a group of 251 adolescent girls. Carriership of the T allele of the MTHFR:С677Т polymorphism was found in 142 children (56.6%), while the homozygous T/T variant was found in 25 girls, or in 10.0% of cases. Compound heterozygosity for the 677CT/1298AC alleles of the MTHFR gene was recorded in 60 individuals, or in 23.9% of cases. Conclusions. The revealed genetic changes in the folate cycle lead to a significant decrease in the activity of methylenetetrahydrofolate reductase, and, accordingly, to an increase in the level of homocysteine in the blood, creating conditions for the occurrence of breast cancer. Given the high level of genetic predisposition, taking into account the constant impact on the body of radioactive elements and their decay products, the occurrence, as a consequence, of serious metabolic disorders, it is necessary to identify the breast cancer risk group of children.

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THE FREQUENCY OF THROMBOTIC COMPLICATIONS AND FEATURES OF GENOTYPES OF POLYMORPHIC MARKERS OF HEMOSTASIS GENES IN CHILDREN WITH NONCOMPACT CARDIOMYOPATHY

Российский педиатрический журнал ◽

10.18821/1560-9561-2017-20-3-139-144 ◽

2019 ◽

Vol 20 (3) ◽

pp. 139-144 ◽

Cited By ~ 2

Author(s):

E. N. Basargina ◽

M. K. Umarova ◽

K. V. Savostyanov ◽

Yu. V. Derevnina ◽

I. E. Smirnov

Keyword(s):

Cardiac Remodeling ◽

Retrospective Cohort ◽

Mthfr Gene ◽

Polymorphic Markers ◽

Chain Reaction ◽

Noncompaction Cardiomyopathy ◽

Thrombotic Complications ◽

Polymerase Chain ◽

The Difference ◽

Folate Cycle

Noncompaction cardiomyopathy (NCMP) is characterized by the anomalous myocardium structure and various types of cardiac remodeling, in some cases it is accompanied by thrombotic complications. Preconditions for thrombosis in the disease are unknown, as also there are differences in thrombosis rates between NCMP and other cardiomyopathies, similarly accompanied by the chronic heart failure and analogous remodeling phenotypes. Aim of study is to reveal the difference in the rate of thrombosis in NCMP and dilated cardiomyopathies (DCMP) in children, and to define differences in the frequency of different genotypes of polymorphic markers in an array of hemostasis genes in the two cardiomyopathies. Methods. There was executed a prospective-retrospective cohort study, included patients from the Cardiac Department of the National Scientific and Practical Center of Children's Health from October 2011 to May 2015. The presence of NCMP was established by echocardiography, alleles and genotypes of polymorphic markers of hemostasis and folate cycle genes were determined by polymerase chain reaction in real-time mode. Results. Thrombotic complications in NCMP children were observed more often than in DCMP cases. There were no differences between NCMP and DCMC patients in the frequency of the polymorphic markers c.1691G>A of the F5 gene (p=0.61) , c.20210G>A of the F2 gene (p=1.0) , c.1565T> C of the ITGB3 gene (p=0.32) , 5G(-675)4G of PLANH1 gene (p=0,52) , G(-455)A of FGB gene (p=0.82) , c.677C>T of MTHFR gene (p=0.11). Conclusion Thrombotic complications in NCMP children occur rather more often than in DCMP cases, studied polymorphic markers of the hemostasis and folate cycle genes do not cause this difference, and this requires continuation of the study.

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PROBLEMS OF EVACUATION HOSPITALS OF THE KRASNOYARSK REGION IN 1941–1943 AND THE CONTRIBUTION OF V. F. VOYNO-YASENETSKY (ST. LUKA)

Bulletin of Kemerovo State University ◽

10.21603/2078-8975-2018-1-46-52 ◽

2018 ◽

pp. 46-52

Author(s):

S. V. Kozhevnikov

Keyword(s):

History Of Medicine ◽

Scientific Work ◽

Hospital System ◽

Great Patriotic War ◽

History Of ◽

Research Goal ◽

The Moment ◽

Key Aspects ◽

The Military ◽

The City

The current paper is the first to present some of the key activities and operational problems of evacuation hospitals in the city of Krasnoyarsk and the whole hospital system of the Krasnoyarsk territory in the first years of the Great Patriotic war. In addition, the paper touches upon the key aspects of the medical, pedagogical and scientific work of the famous surgeon V. F. Voino-Yasenetsky (St. Luka), who worked in Krasnoyarsk evacuation hospitals in 1941 – 1943. The research goal is to reveal the foundations of the diverse activities of evacuation hospitals for the treatment of wounded patients from the moment of their arrival by the military-sanitary trains in the city, further sorting and hospitalization of the wounded into a specialized or General surgical hospital, as well as stressing the importance of the rescue activity conducted by professor and surgeon V. F. Voyno-Yasenetsky in the system of evacuation hospitals. The results of this study can be used by historians of the war period, including those who are involved in the study of history of medicine during the wartime and V. F. Voyno-Yasenetsky's biographers.

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The roles of MTRR and MTHFR gene polymorphisms in congenital heart diseases: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20181160 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 3

Author(s):

Aiping Xu ◽

Weiping Wang ◽

Xiaolei Jiang

Keyword(s):

Gene Polymorphisms ◽

Congenital Heart ◽

Methylenetetrahydrofolate Reductase ◽

Heart Diseases ◽

Meta Analysis ◽

Mthfr Gene ◽

Methionine Synthase ◽

Congenital Heart Diseases ◽

Methionine Synthase Reductase ◽

Study Participants

Background: We performed the present study to better elucidate the correlations of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms with the risk of congenital heart diseases (CHD). Methods: Eligible articles were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations of MTHFR and MTRR gene polymorphisms with CHD. Results: A total of 47 eligible studies were finally included in our meta-analysis. Our overall analyses suggested that MTRR rs1801394, MTRR rs1532268, MTHFR rs1801131 and MTHFR rs1801133 polymorphisms were all significantly associated with the risk of CHD in certain genetic models. Further subgroup analyses according to ethnicity of study participants demonstrated that the MTRR rs1801394 polymorphism was significantly correlated with the risk of CHD only in Asians, whereas MTRR rs1532268, MTHFR rs1801133 and MTHFR rs1801131 polymorphisms were significantly correlated with the risk of CHD in both Asians and Caucasians. Conclusions: Our findings indicated that MTRR rs1532268, MTHFR rs1801131 and MTHFR rs1801133 polymorphisms may affect the risk of CHD in Asians and Caucasians, while the MTRR rs1801394 polymorphism may only affect in risk of CHD in Asians.

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Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults

Blood ◽

10.1182/blood.v101.7.2483 ◽

2003 ◽

Vol 101 (7) ◽

pp. 2483-2488 ◽

Cited By ~ 157

Author(s):

Leo A. J. Kluijtmans ◽

Ian S. Young ◽

Colin A. Boreham ◽

Liam Murray ◽

Dorothy McMaster ◽

...

Keyword(s):

Young Adults ◽

Vitamin B12 ◽

Methylenetetrahydrofolate Reductase ◽

Dietary Factors ◽

Methionine Synthase ◽

Interactive Effects ◽

Serum Folate ◽

Homocysteine Concentration ◽

Functional Polymorphisms ◽

Methionine Synthase Reductase

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine β-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B12, and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between theMTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B12. Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.

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Alzheimer's disease in Brazilian elderly has a relation with homocysteine but not with MTHFR polymorphisms

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2006000600010 ◽

2006 ◽

Vol 64 (4) ◽

pp. 941-945 ◽

Cited By ~ 26

Author(s):

Vanessa Cavalcante da Silva ◽

Flávio José da Costa Ramos ◽

Elizabete Malaquias Freitas ◽

Paulo Roberto de Brito-Marques ◽

Márcia Nery de Holanda Cavalcanti ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mthfr Gene ◽

Plasma Homocysteine ◽

Total Plasma ◽

Chi Square ◽

Coffee Intake ◽

Mthfr Polymorphisms ◽

Homocysteine Concentration ◽

Plasma Homocysteine Concentration

OBJECTIVE: To investigate the association between total plasma homocysteine concentration, C677T and A1298C polymorphisms in MTHFR gene and Alzheimer's disease (AD) development. METHOD: Forty-three patients with probable (63%) and possible (37%) AD and 50 non-demented controls were evaluated. Groups did not differ as to gender, age, scholar years, diabetes, alcohol and coffee intake and physical activity. Total plasma homocysteine (Hcy) levels were determined by HPLC and genotyping for MTHFR by PCR/RFLP. Mann-Whitney "U" test was used to compare quantitative variable, Fisher-Freeman-Halton test to compare genotypes and allele proportions and Chi-square test to other qualitative variables. RESULTS: AD patients presented higher total plasma Hcy levels than controls and the difference was statistically significant. No differences in the C677T and A1298C MTHFR polymorphisms distributions were found between patients and controls. Plasma homocysteine concentration did not change with MTHFR genotypes. CONCLUSION: Our data confirms the association between increased plasma Hcy concentration and AD and suggests that neither C677T nor A1298C MTHFR polymorphisms contributed to genetic susceptibility for AD in elderly individuals in the Northeast of Brazil.

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