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Rev. chil. pediatr ; 91(3): 417-423, jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1126181


Resumen: Introducción: La trombosis senovenosa cerebral neonatal (TSVC), es una patología rara y generalmente grave, de la cual se conoce poco sobre los mecanismos fisiopatológicos responsables y, aunque controvertido, se ha sugerido que la trombofilia genética, puede desempeñar un rol en la patogénesis. Debido a los temores de un sangrado intracraneal el tratamiento anticoagulante con heparina de bajo peso mole cular es controvertido. Objetivo: presentar un recién nacido con una trombosis senovenosa cerebral neonatal, discutir los factores de riesgo trombofílico, y el manejo con heparina de bajo peso molecu lar de la trombosis venosa cerebral. Caso Clínico: Recién nacido de término que debutó a los 8 días de vida con convulsiones clónicas, rechazo al pecho más hipoactividad motora. La neuroimagen con RM mostró una TSVC involucrando múltiples senos venosos, un infarto hemorrágico talámico dere cho y congestión venosa de la sustancia blanca frontal. El estudio de trombofilia puso de relieve una mutación homocigota del gen MTHFR C677T. El tratamiento con heparina de bajo peso molecular se asoció a repermeabilización del seno sagital superior a los 23 días de iniciada la terapia. Conclusio nes: La presentación clínica de la TSVC en el neonato es inespecífica, probablemente en relación con la extensión y gravedad de la lesión y el desarrollo de complicaciones asociadas, como infartos he morrágicos venosos intraparenquimatosos o hemorragia intraventricular. Estas complicaciones son detectables mediante Ecografia o Resonancia Magnética, y deben hacer sospechar una TSVC. En esta experiencia el tratamiento anticoagulante mostró ser seguro y prevenir la extensión de la trombosis.

Abstract: Introduction: Neonatal cerebral sinovenous thrombosis (CSNT) is a rare and generally serious con dition about which there is little knowledge of the responsible pathophysiological mechanisms and, although controversial, it has been suggested that genetic thrombophilia may play a role in its patho genesis. Out of concern for intracranial bleeding, the anticoagulant treatment with low-molecular- weight heparin is controversial. Objective: To present a case of a newborn with neonatal CSNT, to analyze the thrombophilic risk factors, and the management of cerebral venous thrombosis with low-molecular-weight heparin. Clinical Case: Full-term newborn who presented at eight days of life breastfeeding rejection, clonic seizures, and locomotor hypoactivity. The MRI neuroimaging showed a CSNT involving multiple venous sinuses, a right thalamic hemorrhagic infarction, and venous congestion in frontal white matter. Thrombophilia study highlighted a homozygous MTHFR C677T mutation. Treatment with low-molecular-weight heparin was associated with repermeabilization of the superior sagittal sinus after 23 days of starting therapy. Conclusions: The clinical presentation of CSNT in the neonate is nonspecific, probably related to the extent and severity of the injury and the development of associated complications, such as venous hemorrhagic infarctions and intraparenchymal or intraventricular hemorrhage. These complications are detected through ultrasound or MRI, and they should make us suspect a CSNT. In this experience, the anticoagulant treatment proved to be safe and prevents thrombus propagation.

Humans , Female , Infant, Newborn , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/etiology , Enoxaparin/therapeutic use , Methylenetetrahydrofolate Reductase (NADPH2)/deficiency , Homocystinuria/diagnosis , Muscle Spasticity/diagnosis , Anticoagulants/therapeutic use , Psychotic Disorders/complications , Psychotic Disorders/diagnosis , Psychotic Disorders/genetics , Sinus Thrombosis, Intracranial/drug therapy , Genetic Markers , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Homocystinuria/complications , Homocystinuria/genetics , Homozygote , Muscle Spasticity/complications , Muscle Spasticity/genetics , Mutation
Article in Chinese | WPRIM | ID: wpr-826364


To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% 5.0%;=9.874, =0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)μmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)μmol/L](=24.402, <0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)μmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)μmol/L](=12.088, =0.01)and the C/T genotype [(17.80±2.18)μmol/L](=6.496, =0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(=5.655, <0.001)and also significantly lower than those of the C/C genotype(=11.514, <0.001)and the C/T genotype in AS group(=10.287, <0.001). In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.

DNA , DNA Methylation , Genomics , Genotype , Humans , Methylenetetrahydrofolate Reductase (NADPH2) , Polymorphism, Genetic , Spondylitis, Ankylosing
Einstein (Säo Paulo) ; 18: eRC5522, 2020.
Article in English | LILACS | ID: biblio-1142879


ABSTRACT We report a case of a 61-years-old woman in remission of psoriasis for 20 years. She presented recurrence of psoriasis in the form of plaques few days after taking L-methylfolate 15mg/day. The L-methylfolate was prescribed as an adjuvant for the treatment of depression in a patient with the methylenetetrahydrofolate reductase gene polymorphism (MTHFR).

RESUMO Paciente do sexo feminino, 61 anos, em remissão da psoríase por 20 anos. Apresentou recidiva de psoríase em forma de placas poucos dias após início de tratamento L-metilfolato na dose diária de 15mg. O L-metilfolato foi prescrito como terapêutica coadjuvante para tratamento de depressão em paciente portadora do polimorfismo do gene metilenotetrahidrofolato redutase.

Humans , Female , Psoriasis/chemically induced , Quality of Life , Tetrahydrofolates/administration & dosage , Methylenetetrahydrofolate Reductase (NADPH2)/deficiency , Depression/drug therapy , Homocystinuria/complications , Muscle Spasticity/complications , Polymorphism, Genetic , Psychotic Disorders/complications , Recurrence , Tetrahydrofolates/therapeutic use , Treatment Outcome , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged
J. appl. oral sci ; 28: e20190583, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1090773


Abstract Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. Objective: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and −149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. Methodology: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. Results: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. Conclusion: The polymorphism −149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis.

Humans , Male , Female , Adult , Middle Aged , Aged , Periodontitis/genetics , Polymorphism, Genetic , DNA Methylation/genetics , MicroRNAs/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Polymorphism, Restriction Fragment Length , Catalase/genetics , Case-Control Studies , Polymerase Chain Reaction , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Genetic Association Studies , Superoxide Dismutase-1/genetics , Genotype
Arch. endocrinol. metab. (Online) ; 63(3): 280-287, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011172


ABSTRACT Objective Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation that is associated with autoimmune pathology. We investigated the association between MTHFR genetic polymorphisms at g.677C>T and g.1298A>C and their haplotypes, and the risk of thyroid dysfunction among Jordanian females. Subjects and methods A case-control study involving 98 hypothyroidism cases, 66 hyperthyroidism cases and 100 controls was conducted. Polymerase chain reaction/restriction fragment length polymorphism technique was performed to determine genotypes. Statistical analysis using SPSS software was performed. Results Genetic analysis showed a significant difference in genotype frequency of g.1298A>C between cases, and controls [hypothyroidism: AA (45.9%), AC (37.8%), CC (16.3%); hyperthyroidism: AA (9.1%), AC (69.7%), CC (21.2%); controls: AA (37.8%), AC (29.6%), CC (32.7%); CChypo vs. AAhypo: 2.55, 95% CI: (1.18-5.52); OR at least on Chypo: 1.79, 95% CI: (1.07-2.99)]; CChyper vs. AAhyper: 4.01, 95% CI: (1.79-9.01); OR at least on Chyper: 0.18, 95% CI: (0.07-0.48)]. There was no significant difference in genotype frequency of g.677C>T between cases and controls [hypothyroidism: CC (50.0%), CT (32.7%), TT (17.3%); hyperthyroidism: CC (77.3%), CT (15.2%), TT (7.6%); controls: CC (55.6%), CT (32.3%), TT (12.1%)]. There was a significant difference of MTHFR haplotypes among hypothyroidism cases and controls. TA and CC had a lower hypothyroidism risk whereas; TC showed a higher risk. Conclusions g.1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease. CC, TA, and TC haplotypes affect the risk of hypothyroidism. Larger samples should be included in the future to verify the role of MTHFR polymorphisms in thyroid diseases.

Humans , Female , Adult , Middle Aged , Young Adult , Polymorphism, Restriction Fragment Length/genetics , Polymorphism, Single Nucleotide/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Hyperthyroidism/genetics , Hypothyroidism/genetics , Haplotypes , Case-Control Studies , Polymerase Chain Reaction , Risk Factors , DNA Methylation , Genetic Predisposition to Disease , Alleles , Genotype , Jordan
Pesqui. bras. odontopediatria clín. integr ; 19(1): 3962, 01 Fevereiro 2019. ilus, tab
Article in English | LILACS, BBO | ID: biblio-997961


Objective: To evaluate the inclusion capacity and bactericidal efficiency of diallyl dimethyl ammonium chloride (PDADMAC) diluted in tetrahydrofuran (THF) upon inclusion in the medical grade silicone polymer structure. Material and Methods: It was diluted the PDADMAC in THF at the concentration of 4wt%. It was included in the silicon paste during its vulcanization process. The contact angle measurements were performed to evaluate whether the biocide inclusion into the silicon paste was successful. All samples were sterilized with gamma radiation at 25KGy-dosage prior to the microbiological tests. Microbiological testing strictly followed the Antibacterial products - Test for antibacterial activity and efficacy JIS Z 2801: 201010 and the used of specific bacteria, as Staphylococcus aureus ATCC 6538P and Escherichia coli ATCC 8739. Results: The results showed that PDADMAC, when dissolved in THF at 4wt%, displayed good incorporation in medical silicone and a broad-spectrum antibacterial response. The results of the tests using Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538P showed that the silicone with no biocide addition did not present antibacterial activity. In contrast, the experimental group plus 2 mL of PDADMAC would have an ideal antibacterial response. Conclusion: Medical grade silicone can be used as a material with antibacterial properties, since it has been able to keep PDADMAC compound attached to its structure, thus acquiring antimicrobial property.

Silicone Elastomers/analysis , In Vitro Techniques/methods , Maxillofacial Prosthesis , Anti-Bacterial Agents/analysis , Silicone Elastomers , Brazil , Dental Materials , Methylenetetrahydrofolate Reductase (NADPH2)
Arch. endocrinol. metab. (Online) ; 62(1): 21-26, Jan.-Feb. 2018. tab
Article in English | LILACS | ID: biblio-887636


ABSTRACT Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Polymorphism, Genetic/genetics , Peptidyl-Dipeptidase A/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Diabetes Mellitus, Type 2/enzymology , Obesity/complications , Brazil , Case-Control Studies , Polymerase Chain Reaction , Risk Factors , Mutagenesis, Insertional , Gene Deletion , Genetic Predisposition to Disease , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Genotype , Obesity/enzymology
Article in Korean | WPRIM | ID: wpr-718773


Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.

Achondroplasia , Acidosis, Lactic , Angelman Syndrome , Apolipoproteins , Brain Diseases , Breast , Deafness , Education , Epilepsies, Myoclonic , Fragile X Syndrome , Gene Rearrangement , Hearing Loss , Hepatolenticular Degeneration , Huntington Disease , Janus Kinase 2 , Korea , Laboratory Proficiency Testing , Leukemia , Li-Fraumeni Syndrome , Methylenetetrahydrofolate Reductase (NADPH2) , Molecular Biology , Multiple Endocrine Neoplasia , Muscular Atrophy, Spinal , Muscular Disorders, Atrophic , Muscular Dystrophy, Duchenne , Optic Atrophy, Hereditary, Leber , Ovarian Neoplasms , Pathology, Molecular , Phosphotransferases , Quality Control , Quality Improvement , Spinocerebellar Ataxias , Vascular Endothelial Growth Factor Receptor-1
Article in English | WPRIM | ID: wpr-772968


The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.

Asian Continental Ancestry Group , Genetics , China , Ethnology , Cleft Lip , Genetics , Cleft Palate , Genetics , Genome-Wide Association Study , Humans , Infant , Logistic Models , Machine Learning , Methylenetetrahydrofolate Reductase (NADPH2) , Genetics , Polymorphism, Single Nucleotide , Retinol-Binding Proteins, Plasma , Genetics , Risk Assessment
Rev. bras. ginecol. obstet ; 39(12): 659-662, Dec. 2017. tab
Article in English | LILACS | ID: biblio-898850


Abstract Introduction The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods This case-control study included 130 infertile women consulting at a private clinic betweenMarch 2003 andMarch 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results The frequency of the mutation was of 58.5% for the case group (n = 76) and of 49.2% for the fertile controls (n = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when themutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility.

Resumo Introdução A importância da mutação C677T no gene da metilenotetrahidrofolato redutase (MTHFR) em mulheres com infertilidade permanece controversa. Objetivo Avaliar se a mutação MTHFR C677Témais frequente em mulheres inférteis, e se pode ser associada com a ocorrência de infertilidade na população brasileira. Métodos Estudo de caso-controle, com avaliação de 130 mulheres com infertilidade atendidas em clínica privada no período de março de 2003 a março de 2005 (dados previamente publicados) e 260 mulheres férteis atendidas no ambulatório de planejamento familiar de nossa instituição no período de abril de 2012 a março de 2013. Análise dos dados Foram utilizados os testes de Qui-quadrado e Exato de Fisher para o estudo da associação entre a presença damutação MTHFR C677T e o antecedente de infertilidade. Resultados A frequência da mutação foi de 58,5% nos casos (n = 76) e de 49,2% nos controles (n = 128). Dentre os casos, 13 apresentavam esta mutação em homozigose (10%). Nos controles, a homozigose foi encontrada em 23 mulheres férteis (8,8%). Estas diferenças não foram estatisticamente significativas. Conclusões Este estudo sugere que a presença da mutação MTHFR C677T não constitui fator de risco para infertilidade, mesmo em casos de homozigose. Estudos complementares são necessários para ratificar se a investigação desta mutação deve ser considerada desnecessária em mulheres com infertilidade.

Humans , Female , Adult , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Fertility/genetics , Infertility, Female/genetics , Mutation , Case-Control Studies , Risk Factors
An. bras. dermatol ; 92(6): 793-800, Nov.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-887112


Abstract: Background: epigenomes can be influenced by environmental factors leading to the development of diseases. Objective: To investigate the influence of sun exposure on global DNA methylation and hydroxymethylation status and at specific sites of the miR-9-1, miR-9-3 and MTHFR genes in skin samples of subjects with no history of skin diseases. Methods: Skin samples were obtained by punch on sun-exposed and sun-protected arm areas from 24 corpses of 16-89 years of age. Genomic DNA was extracted from skin samples that were ranked according to Fitzpatrick's criteria as light, moderate, and dark brown. Global DNA methylation and hydroxymethylation and DNA methylation analyses at specific sites were performed using ELISA and MSP, respectively. Results: No significant differences in global DNA methylation and hydroxymethylation levels were found among the skin areas, skin types, or age. However, gender-related differences were detected, where women showed higher methylation levels. Global DNA methylation levels were higher than hydroxymethylation levels, and the levels of these DNA modifications correlated in skin tissue. For specific sites, no differences among the areas were detected. Additional analyses showed no differences in the methylation status when age, gender, and skin type were considered; however, the methylation status of the miR-9-1 gene seems to be gender related. Study limitations: there was no separation of dermis and epidermis and low sample size. Conclusion: sun exposure does not induce changes in the DNA methylation and hydroxymethylation status or in miR-9-1, miR-9-3 and MTHFR genes for the studied skin types.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Skin/radiation effects , Skin Diseases/etiology , Sunlight/adverse effects , DNA Methylation/genetics , Reference Values , Skin/chemistry , Enzyme-Linked Immunosorbent Assay , Sex Factors , Polymerase Chain Reaction , Age Factors , Radiation Exposure , MicroRNAs/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Epigenomics
Article in English | WPRIM | ID: wpr-116476


Hyperuricemia is related to metabolic syndrome, and is defined as an over-production or under-excretion of uric acid (UA), with increased UA serum concentration. Among other causes, Hyper-homocysteinemia (H-Hcy) can be responsible for hyperuricemia. The mechanisms underlying the association between these two conditions are unclear, but increased UA serum levels can be a consequence of renovascular atherosclerosis, with reduced UA excretion. An alternative hypothesis is the over-production of UA from adenosine (originating from S-adenosyl-homocysteine). Genetic polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) may contribute. A possible mechanism is purines biosyinthesis originating from this gene variant. However, the results obtained from several studies and meta-analyses of the relationship between H-Hcy and hyperuricemia are ambivalent, and broader research is needed.

Adenosine , Atherosclerosis , Homocysteine , Hyperuricemia , Methylenetetrahydrofolate Reductase (NADPH2) , Polymorphism, Genetic , Purines , Uric Acid
Article in English | WPRIM | ID: wpr-219265


OBJECTIVE: To identify the associations between polymorphisms of the 3′-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. METHODS: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C>A, 4869C>G, 5488C>T, and 6685T>C 3′-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry. RESULTS: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178–0.994; p=0.048) for RPL. Analysis of variance revealed that MTHFR 4869C>G was associated with altered CD56⁺ natural killer cell percentages (CC, 17.91%±8.04%; CG, 12.67%±4.64%; p=0.024) and folate levels (CC, 12.01±7.18 mg/mL; CG, 22.15±26.25 mg/mL; p=0.006). CONCLUSION: Variants in the 3′-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.

Biomarkers , Discrimination, Psychological , Female , Flow Cytometry , Folic Acid , Haplotypes , Humans , Killer Cells, Natural , Metabolism , Methylenetetrahydrofolate Reductase (NADPH2) , Odds Ratio , Pregnancy
Article in English | WPRIM | ID: wpr-158113


The balance between coagulation and fibrinolysis is an essential part in early pregnancy. Mutations in methylenetetrahydrofolate reductase (MTHFR) gene lead to decreased activity of the enzyme and hyperhomocysteinemia, which then induces platelet aggregation by promoting endothelial oxidative damage, possibly resulting in adverse effect on maintenance of pregnancy. We investigated the role of MTHFR single nucleotide polymorphisms (SNPs), C677T and A1298C, in Korean patients with recurrent pregnancy loss (RPL). We conducted a prospective case-control study in the Korean population. Subjects included 302 women with 2 or more consecutive, unexplained, spontaneous miscarriages before 20 weeks of gestation and 315 control women without a history of recurrent miscarriages. The genotyping for C677T and A1298C polymorphisms was performed using the TaqMan assay. Continuous variables were compared using Student's t-test, and χ² test was used to evaluate differences in the genotype distributions between the RPL and the controls. The genotype distribution of both polymorphisms in the RPL group did not differ from those of the controls. For further analysis, if RPL patients were divided according to the numbers of pregnancy losses (≥ 2 and ≥ 3) neither group was significantly different compared with controls. MTHFR gene C677T and A1298C polymorphisms are not associated with idiopathic RPL in Korean women, suggesting that those may not be susceptible allelic variants or be deficient to cause RPL.

Abortion, Habitual , Abortion, Spontaneous , Case-Control Studies , Female , Fibrinolysis , Genotype , Humans , Hyperhomocysteinemia , Methylenetetrahydrofolate Reductase (NADPH2) , Platelet Aggregation , Polymorphism, Single Nucleotide , Pregnancy , Prospective Studies
Article in Chinese | WPRIM | ID: wpr-344148


<p><b>OBJECTIVE</b>To investigate the effect of MTHFR gene on schizophrenia and its cognitive function.</p><p><b>METHODS</b>We recruited 254 schizophrenia patients with stable condition, 339 healthy controls for genetic analysis and 72 healthy controls for cognitive evaluation. The repeatable battery for the assessment of neuropsychological status (RBANS) was used for cognitive measurement. PCR-RFLP technique was carried out to genotype 677C/T polymorphism.</p><p><b>RESULTS</b>There were no significant differences in genotypic or allelic frequencies of the 677C/T polymorphism between the case and control groups (P> 0.05). In the RBANS, patients had higher scores of immediate memory, visuospatial skill, language, attention, delayed memory and total scores than healthy controls (P< 0.01); Patients with different genotypes of 677C/T polymorphism had significant differences in the scores of immediate memory, attention and total scores (P< 0.05).</p><p><b>CONCLUSION</b>Our results did not provide evidence for MTHFR gene conferring susceptibility to schizophrenia. However, there was a significant association between the MTHFR gene and cognitive impairment in patients with schizophrenia, especially in immediate memory and attention.</p>

Adolescent , Adult , Cognition , Genotype , Humans , Methylenetetrahydrofolate Reductase (NADPH2) , Genetics , Middle Aged , Polymorphism, Genetic , Schizophrenia , Genetics , Schizophrenic Psychology , Young Adult
Article in English | WPRIM | ID: wpr-226318


BACKGROUND: Chemopreventive effects and the underlying mechanisms of blueberry (Vaccinium spp.) are not clearly understood in human. We hypothesized blueberry would work via antioxidative and epigenetic modulation, which is similar to vitamin C. METHODS: We performed a pilot and non-inferiority study in healthy young women (n = 12), who consumed vitamin C (1 g/d) or 240 mL of blueberry juice (total polyphenols 300 mg and proanthocyanidin 76 mg/d) for 2 weeks. We analyzed 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in their urine, and global and specific DNA methylation at the NAD(P)H quinone oxidoreductase 1 (NQO1), methylenetetrahydrofolate reductase (MTHFR), or DNA methyltransferase 1 (DNMT1) genes in their blood. RESULTS: Urinary 8-OHdG levels were reduced by blueberry consumption rather than by vitamin C. The methylation (%) of the MTHFR was significantly decreased in blueberry-consumers and the antioxidant-susceptible subgroup, whose urinary MDA levels were decreased by the intervention. We also found a positive correlation between changes of urinary 8-OHdG and of DNA methylation at the MTHFR or the DNMT1 (P < 0.05). However, the genetic polymorphism of the MTHFR (C677T in exon 4) did not affect any above markers. CONCLUSIONS: Blueberry juice shows similar anti-oxidative or anti-premutagenic activity to vitamin C and the potential as a methylation inhibitor for the MTHFR and the DNMT1 in human.

Ascorbic Acid , Blueberry Plants , DNA , DNA Methylation , Epigenomics , Exons , Female , Humans , Malondialdehyde , Methylation , Methylenetetrahydrofolate Reductase (NADPH2) , Oxidative Stress , Polymorphism, Genetic , Polyphenols , Vitamins
Egyptian Journal of Medical Human Genetics [The]. 2017; 18 (1): 9-18
in English | IMEMR | ID: emr-189211


Background: Methylenetetrahydrofolate reductase [MTHFR] is an important enzyme of folate/homocysteine pathway and is essential for DNA synthesis and methylation. MTHFR gene polymorphisms have been reported as risk factors for congenital defects and several metabolic and neurological disorders. Several studies have investigated an association between maternal MTHFR A1298C polymorphism and Down syndrome [DS] child. However, results have been inconclusive

Aim: A meta-analysis of published case-control studies up to December, 2015 was performed to investigate this association

Methods: Electronic databases were searched for case-control studies and odds ratios [ORs] with 95% confidence intervals [CIs] were estimated to assess the association. Total twenty-one case-control studies with 2004 cases and 2523 controls were included in the present meta-analysis

Results: Results of meta-analysis showed a significant association between maternal A1298C polymorphism and DS pregnancy with homozygote model [CC vs. AA: OR= 1.26, 95% CI= 1.01-1.58, p=0.04], but no such association was found in any other genetic models [C vs. A: OR =1.07, 95% CI= 0.93-1.23, p=0.32; CC + AC vs. AA: OR =1.08, 95% CI= 0.96-1.23, p=0.18; CC vs. AC+ AA: OR = 1.11, 95% CI= 0.90-1.36, p=0.30; AC vs. AA: OR =1.06, 95% CI= 0.93-1.21, p= 0.34]

Conclusion: Subgroup and sensitivity analysis results showed that this polymorphism is a risk factor for DS pregnancy in Asian populations but not in Caucasian population as well as in overall meta-analysis

Humans , Female , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Pregnancy , Folic Acid , Homocysteine , Meta-Analysis as Topic , Case-Control Studies
Egyptian Journal of Hospital Medicine [The]. 2017; 67 (2): 628-634
in English | IMEMR | ID: emr-188448


Purpose: To assess MTHFR rs 1801133 [C677T] gene polymorphism in diabetic patients as a risk factor for diabetic retinopathy and to establish the changes in Platelet indices and count in diabetic patient as compared to the healthy control group

Patients and Methods: The study included 40 patients with Type 2 Diabetes Mellitus. They were divided into 2 equal groups, 20 patients with Diabetic Retinopathy, 20 patients without Diabetic Retinopathy. Patients were selected from those attending the outpatient Ophthalmology Unit and Diabetes Clinic of Al-Zahraa University Hospital in the period from June 2014 to June 2015. Their ages ranged between 34 to 66 years old

They were 14 males and 26 females. Twenty cases apparently healthy individuals were selected as a control group. All cases were subjected to full history taking and complete ophthalmological examination. Also laboratory investigations were done including complete blood picture, kidney and liver function tests, coagulation profile, urine analysis, lipid profile, fasting and postprandial blood sugar and Genetic study for detection of MTHFR gene C677T mutation [rs 1801133] by real time PCR

Results: In all diabetic patients the mutant homozygous TT showed a highly statistically significant increase in FBS [p=0.000], PPBS [p=0.000], HbAlC [p=0.000] and cholesterol [p=0.001] as compared to wild type. Also in all diabetic patients the mutant homozygous TT showed a highly statistically significant increase in FBS [p=0.002], PPBS [p=0.001], HbAlC [p=0.019] and cholesterol [p=0.012] as compared to heterozygous mutant type

Conclusion: The homozygous mutant type [TT] of rs!801133 was detected in 10% of DR patients group while absent in DWR group and the control group. The heterozygous mutant type [CT] was increased in DR group [50%] as compared to DWR group [35%] and the control group [25%]

Humans , Female , Male , Adult , Middle Aged , Methylenetetrahydrofolate Reductase (NADPH2) , Polymorphism, Genetic , Diabetes Mellitus, Type 2/genetics , Risk Factors , Blood Platelets
Rev. chil. nutr ; 43(4): 336-345, dic. 2016. ilus, tab
Article in Spanish | LILACS | ID: biblio-844484


Folate is an essential nutrient because mammals lack biological activity to synthesize. It different factors generate folate deficiency. Recent studies have identified that the C677T variant of the enzyme methylene tetrahydrofolate reductase (MTHFR), can play a role in serum folate concentrations (SFC) and red cell folate (RCF). The aim of this rewiev was to actualice some generalities of folate metabolism, factors related to its deficiency biochemical indicators used to assess the nutritional status of folate and role of the C677T polymorphism of the MTHFR enzyme on the cycle of folate and methionine. It is necessary to design studies with representative samples corroborating the effect of polymorphisms on biochemical indicators of nutritional status of folate and determine the dose-response effect and contribute to modify the nutritional recommendations with the necessary scientific evidence.

El folato es un nutriente esencial porque los mamíferos carecen de actividad biológica para sintetizarlo. Diferentes factores generar deficiencia de folato. Estudios recientes han identificado que la variante C677T de la enzima metilen tetrahidrofolato reductasa (MTHFR), puede jugar un papel en las concentraciones de folato sérico (FS) y eritrocitario (FE). El objetivo de este trabajo fue revisar algunas generalidades del folato, su metabolismo, los factores relacionados con su deficiencia, los indicadores bioquímicos utilizados para evaluar el estado nutricional del folato y el papel del polimorfismo C677T de la enzima MTHFR sobre el ciclo del folato y de la metionina. Es necesario diseñar estudios con muestras representativas que corroboren el efecto de los polimorfismos sobre los indicadores bioquímicos del estado nutricional del folato y determinar el efecto dosis-respuesta y así contribuir con la evidencia científica necesaria para modificar las recomendaciones nutricionales.

Humans , Vitamin B 12 , Food , Methylenetetrahydrofolate Reductase (NADPH2) , Enzymes