Polimorfismo de proteína 5, 10-metilentetrahidrofolatoreductasa en población venezolana / Polymorphisms proteína 5, 10-metilentetrahidrofolatoreductasa in venezuelan people

El folato es un miembro del grupo de la vitamina B y está relacionado con enfermedades crónicas como anemia megaloblástica, enfermedad cardiovascular, cáncer, disfunción cognitiva y riesgo de defectos del tubo neural. La proteína 5,10-metilentetrahidrofolato reductasa (MTHFR) juega un papel clave en el metabolismo del folato mediante la síntesis de nucleótidos y reacciones de metilación. El gen MTHFR se encuentra en el cromosoma 1 (1p36.3), y se han descrito dos alelos comunes, el alelo C677T (termolábil) y el alelo A1298C.El objetivo de este estudio es evaluar la distribución de los polimorfismos genéticos en MTHFR C677T y A1298C en la población venezolana. METODOS: estudio de tipo transversal, descriptivo, experimental y correlacional Las muestras de sangre se colectaron en 314 donantes no emparentados y sanos de la población. Los polimorfismos de un solo nucleótido(SNP) MTHFR 677C>T y 1298A>C se analizaron mediante polimorfismo de longitud de fragmento de restricción de reacción en cadena de polimerasa (PCR-RFLP). El desequilibrio de ligamiento (LD) entre pares de SNP se calculó mediante la prueba X. usando Prism 5 (GraphPad software, Inc). RESULTADOS: Encontramos mayor frecuencia genotípica de heterocigotos para el polimorfismo MTHFR C677T en la población general venezolana, con excepción del grupo caucásico. El polimorfismo MTHFR A1298C en el 70%de la población de estudio es homocigoto de tipo salvaje, encontrándose una baja frecuencia de homocigoto mutado. CONCLUSIONES: Se encontraron diferencias significativas entre grupos étnicos, destacando la importancia del genotipado racial de estos polimorfismos en la población venezolana(AU)

Folate is a member of the vitamin B and it has also been indicated that may be related to chronic diseases such as megaloblastic anemia, cardiovascular disease, cognitive dysfunction and risk of neural tube. Methylenetetrahydro folatereductase (MTHFR) is a key enzyme of folate pathway by nucleotide synthesis and methylation reactions. Several polymorphisms were reported in MTHFR gene but C677Tand A1298 polymorphism are most studied and these have been reported to be risk factor for several diseases/disorders. The present study was designed to determine the frequency of MTHFR polymorphisms in Venezuelan healthy population. METHODS: The blood samples were collected from 314 unrelated and healthy donors from population. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through the .. test using Prism 5 (GraphPad sftoware, Inc). RESULTS: We find higher genotypic frequency of heterozygotes for the MTHFR C677T polymorphism in the Venezuelan general population, with the exception of the Caucasian group. MTHFR A1298C polymorphism in 70%of the study population is homozygous wild type, finding alow frequency of homozygous mutated. CONCLUSIONS: Significant differences between ethnic groups were found,highlighting the importance of racial genotyping of these polymorphisms in the Venezuelan population(AU)

Study on the relationship between recurrent spontaneous abortion and methylene tetrahydrofolate reductase, plasminogen activator inhibitor-1 gene polymorphism and serum folate concentration in pregnant women of appropriate age / 中国综合临床

Objective:To investigate the association between recurrent spontaneous abortion (RSA) and methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphism in pregnant women of appropriate age, and to observe the difference of the serum concentration of patients with different MTHFR genotypes after taking different does of folic acid.Methods:A prospective case-control study was conducted, one handred and eleven pregnant women with a history of unexplained RSA and gestation less than 12 weeks who visited the Department of Obstetrics and Gynecology of Xuancheng People's Hospital of Anhui Province from January 2019 to June 2021 were enrolled into the RSA group, and 100 normal women of childbearing age in the same area with no history of abortion were included in the control group. After venous blood was extracted, the polymorphisms of MTHFR gene C677T, A1298C PAI-1 and the serum folic acid concentration were detected.The comparison between the measurement data groups with normal distribution adopts t-test, and the counting data adopts t-test χ 2 test, Logistic regression analysis was used for multivariate analysis. Results:The genotype and allele of MTHFR C677T (CC:21.62%(24/111) and 51.00%(51/100), TT: 28.83%(32/111) and 12%(12/100)) and allele (C: 46.40%(103/222) and 69.50% (139/200), T: 53.60%(119/222) and 30.50%(61/200)) and PAI-1 (5G5G: 22.52%(25/111) and 48.00%(48/100), 4G4G: 44.14%(49/111)and 16.00%(16/100); 5G: 39.19%(87/222) and 66.00%(132/200), 4G: 60.81%(135/222) and 34.00%(68/200)) were significantly different (χ 2 values were 21.82, 22.96 and 23.51, 30.30; all P <0.001) between the RSA group and control group. Logistic analysis showed that MTHFR C677T ( OR=0.477, 95% CI 0.303-0.750) and PAI-1 genotype ( OR=0.451, 95% CI 0.306-0.665) were closely related to recurrent abortion ( P=0.001 and P<0.001). There were no significant differences in genotype and allele of MTHFR A1298C between the two groups ( P values were 0.270 and 0.149).There was no significant difference in serum concentration of folic acid between the two groups ( P=0.355 for 0.4 mg folic acid and P=0.786 for 0.8 mg or more folic acid) at the same dose of folic acid. Conclusion:The occurrence of recurrent spontaneous abortion in women of childbearing age may be related to MTHFR C677T and PAI-1 site mutation, and may not be related to MTHFR A1298C site mutation.

Thromboelastogram parameters and MTHFR gene polymorphism in the diagnosis of adverse fetal pregnancy outcomes / 中国输血杂志

【Objective】 To retrospectively analyze the situation of patients with adverse fetal outcomes by thromboelastogram (TEG) parameters and, MTHFR gene polymorphism, so as to provide molecular biological diagnosis basis for patients with adverse pregnancy outcomes, and a new scheme for early prevention and treatment of women of childbearing age with MTHFR gene polymorphism. 【Methods】 A total of 100 women with adverse fetal pregnancy outcomes were selected as the adverse pregnancy group, and 100 healthy women of childbearing age with normal pregnancy history were selected as the controls. MTHFR gene C677T and A1298C polymorphisms were detected by polymerase chain reaction (PCR). TEG and blood coagulation were detected in the experimental group. 【Results】 The A1298C gene polymorphism(AA、CC、AC; A、C) was similar in both adverse pregnancy group and the controls. The frequency distribution of C, T allele of MTHFR gene C677T was statistically significant (χ2=4.60, P<0.05, OR =1.645, 95% CI: 1.042~2.595). TT and CT+ CC types showed significant different association with the factors of stillbirth(χ2 =7.49, P<0.05). MA value of TEG in the diagnosis of TT type of C677T genotypes MTHFR in 32 patients with adverse pregnancy outcome was analyzed. The area under the AUC curve of MA value was 0.795. 【Conclusion】 MTHFR C677T polymorphism TT with TEG parameter hypercoagulability is an important risk factor in the occurrence of pregnancy stillbirth in adverse pregnancy outcomes.

Trombosis senovenosa cerebral en un recién nacido con mutación MTHFR C677T tratado con enoxaparina / Cerebral sinovenous thrombosis in a newborn with mutation of MTHFR C677T treated with enoxaparin

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.

Prevalence of the MTHFR C677T Mutation in Fertile and Infertile Women / Prevalência da mutação MTHFR C677T em mulheres férteis e inférteis

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.

MTHFR C677T and A1298C Gene Polymorphisms and Ischemic Heart Disease (IHD) in a Sri Lankan Population - A Preliminary Study

MTHFR A1298C and C677T SNPs are now recognised as important genetic mutations which would give rise to hyperhomocysteinemia. In this study, we analysed the prevalence of these two SNPs in 79 ischemic heart disease (IHD) patients awaiting coronary artery bypass grafting and 79 healthy subjects. MHFR polymorphisms were analysed using polymerase chain reaction followed by a restriction fragment analysis. Prevalence rates for MTHFR C677T polymorphism were 72.8%, 24.7%, and 2.5% for CC, CT, and TT genotypes, respectively, for the whole study population with 677CC genotype being the predominant genotype among both the IHD patients and the controls. The 677TT genotype was detected only among the IHD patients. There was no significant difference in MTHFR 677 genotype variations between IHD patients and the control group. Prevalence rates for the MTHFR A1298C polymorphism were 50%, 37.3%, and 12.7% for the AA, AC, and CC genotypes, respectively, for the whole study population with 1298AA genotype being the predominant genotype among controls and 1298AC the predominant genotype among IHD patients. There was a significant difference (p < 0.01) between IHD patients and controls when the MTHFR 1298 genotype variations were compared. Allele frequencies for the mutant T allele for C677T mutation at 0.149 are the highest reported from Sri Lanka. The frequency of the C for the A1298C mutation was 0.313. Results of this study indicate that MTHFR A1298C SNP is more prevalent in Sri Lankans when compared to C677T SNP and that the mutant forms of the MTHFR A1298C SNP are associated with ischemic heart disease.

The gene polymorphisms of MTHFR C677T and the susceptibility of chronic pulmonary heart disease / 天津医药

Objective To investigate the relationship between gene polymorphisms of homocysteine (Hcy), metabolic enzymes methylenetetrahydrofolate reductase MTHFR C677T and chronic pulmonary heart disease (CPHD). Methods The gene polymorphisms of MTHFR C677T were determined by the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)in CPHD patients (n=120) and healthy control (HC, n=120), and genotyping was carried on. The automatic biochemistry analyzer was used to detect the level of Hcy and other related biochemical indicators. Results There was significant difference in Hcy level between the CPHD group and HC group (P<0.05). The mutation frequencies of CC, CT and TT were 24.17%, 43.33%and 32.50%, 35.00%, 47.50%and 17.50%in the CPHD group and HC group. The mutation frequencies of allele C/T were 45.83%and 54.17%in HC group, and 58.75%and 41.25%in control group. There was significant difference in the overall frequency distribution between the three genotypes (χ2 =8.010, P<0.05). The frequency of T allele was significantly higher in CPHD group than that in control group (χ2=8.025,P<0.05). Conclusion The increased Hcy and its metabolic enzyme MTHFR C677T may be involved in the occurrence and development of CPHD.

Hyper-homocysteinemia Inducing Hyperuricemia: What are the Mechanisms?

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.

Methylene tetrahydrofolate reductase, transforming growth factor-ß1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis / Polimorfismos dos genes metilenotetrahidrofolato redutase, fator de crescimento transformador β1 e linfotoxina-α e susceptibilidade à artrite reumatoide

ABSTRACT Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population.

RESUMO Antecedentes: A artrite reumatoide é uma doença autoimune amplamente prevalente com sugerida predisposição genética. Objetivos: Detectar o padrão de polimorfismo dos genes metilenotetrahidrofolato redutase (MTHFR C677 T e A1298 C), fator de crescimento transformador β1 (TGF-β1 T869 C) e linfotoxina-α (LT-α A252G) em pacientes com artrite reumatoide e correlacionar esses padrões com a atividade da doença e os níveis séricos de fator de necrose tumoral alfa (TNF-α), fator ativador de linfócitos B (BAFF) e osteopontina. Métodos: Foram genotipados 194 indivíduos – 90 controles e 104 com artrite reumatoide – à procura de polimorfismos dos genes MTHFR C677 T e A1298 C, TGF-β1 T869 C e LT-α A252G com uma metodologia baseada na PCR-RFLP. Mensuraram-se também os níveis séricos de TNF-α, osteopontina e BAFF com kits de Elisa. Resultados: O genótipo CT e o alelo T do MTHFR C677 T e o genótipo GG e alelo G do LT-α A252G estão associados ao risco de AR e a níveis mais elevados da citocina pró-inflamatória TNF-α em pacientes com artrite reumatoide. Conclusão Os achados do presente estudo sugerem que há associação entre os polimorfismos dos genes MTHFR C677 T e LT-α A252G e um risco aumentado de AR nessa amostra da população egípcia.

Detection and analysis of plasma homocysteine levels and its metabolism related indicators in patients with primary angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

?AIM: To explore the relation of homocysteine ( Hcy ) and its metabolic related indicators with primary angle-closure glaucoma ( PACG) .?METHODS: In this study, a total of 150 PACG patients and 150 controls were enrolled. The patients with PACG were diagnosed by applanation tonometer, Humphrey perimetry ( HVF ) , optical coherence tomography ( OCT ) , gonioscope. The normal controls were recruited from physical examination center. Blood samples were collected and the plasma was used to determine homocysteine, vitamin B12 and folic acid. DNA was extracted to determine the methylenetetrahydrofolate reductase ( MTHFR ) C677TT genotype and gene polymorphism.?RESULTS:There was a statistically significant difference (t=2. 04,P=0. 04) in mean homocysteine levels between patients with PACG ( 16. 11 ± 1. 66μmol/L ) and controls (15. 74± 1. 52μmol/L). The level of vitamin B12 in PACG group was 248. 09 ± 119. 07pg/mL and the control group was 230. 21 ± 142. 93pg/mL. No statistically significant difference was found on the vitamin B12 level between the two groups ( t = 0. 84, P = 0. 40 ). The folic acid levels showed no statistically significant differences( t=1. 65,P=0.17) between the PACG group(12. 02±7. 81ng/mL) and the control group (13. 15 ± 6. 25ng/mL). The frequency distribution of the MTHFR C677T genotypes was found to be significantly associated (χ2 =6. 2,P<0. 05) with PCAG (CC 84. 7%, CT 4. 7%, TT 10. 7%) as compared to the controls (CC 94. 7%, CT 2. 0%, TT 3. 3%). The frequency distribution of TT genotypes of MTHFR C677T in the PACG group was significantly higher than that in the control group. Moreover, our findings showed significant difference (χ2=14. 2,P<0. 05) between the allele frequency of the C677T single nucleotide polymorphism within the MTHFR gene in POAG patients ( T 87. 0%, C 13. 0%) and the control group(T 95. 7%,C 4. 3%) .?CONCLUSION: These results show that the Hcy level and the TT genotypes of MTHFR C677T were higher in the PACG patients than in controls. Therefore, our data suggests that high Hcy level and the related indicators are associated with high PACG risk.

Potential Risk Factors Associated With Vascular Diseases in Patients Receiving Treatment for Hypertension

BACKGROUND: Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. METHODS: A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. RESULTS: All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. CONCLUSIONS: The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.

Polimorfismo C677T de la enzima 5, 10-metilenetetrahidrofolato reductasa (MTHFR) y enfermedad cardiovascular / C677T polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) and cardiovascular disease

Introducción: existe evidencia sobre la relación entre niveles elevados de homocisteína (Hcy) en plasma y riesgo de enfermedad cardiovascular (ECV). El polimorfismo C677T del gen que codifica la enzima 5,10-metilenetetrahidrofolato reductasa (MTHFR) es considerado un determinante genético para la concentración de homocisteína. Vitaminas como el ácido fólico, B12, B2 y B6 participan en el metabolismo de este aminoácido. Objetivo: explorar la evidencia bibliográfica sobre el polimorfismo C677T, el riesgo de enfermedad cardiovascular y aquellos nutrientes que puedan prevenirla.Materiales y Método: se realizó una búsqueda de publicaciones en bases de datos electrónicas MEDLINE, EMBASE y Google académico. Se incluyeron aquellos artículos que contenían las palabras claves o una combinación de ellas, durante 1994-2015. Resultados: 15 artículos fueron incluidos. Se evidenció un aumento del riesgo de ECV en portadores del polimorfismo C677T. El ácido fólico es un importante determinante de la concentración de Hcy en plasma. Portadores homocigotos TT mostraron una disminución del nivel de Hcy en respuesta a la suplementación con vitaminas B12, B2 y B6.Conclusión: los trabajos analizados mostraron la relación entre la menor actividad de la enzima MTHFR, el incremento de Hcy y el riesgo de ECV. Los valores de Hcy en plasma se vieron influenciados por deficiencias de vitaminas del grupo B, siendo éstas un importante determinante de su concentración plasmática en el genotipo TT.

Polimorfismo C677T del gen de la metilentetrahidrofolato reductasa en madres de niños afectados con defectos del tubo neural / C677T polymorphism of the methylentetrahydrofolate reductase gene in mothers of children affected with neural tube defects.

Los defectos del tubo neural (DTN) son las alteraciones congénitas más frecuentes del sistema nervioso central. El mecanismo de transmisión hereditario de los DTN aislados es multifactorial, se debe a la interacción de factores ambientales y genéticos. El polimorfismo 677C>T del gen de la metilentetrahidrofolato reductasa (MTHFR) ha sido implicado como factor de riesgo para DTN. El objetivo de este trabajo fue investigar la asociación del polimorfismo 677C>T del gen de la MTHFR como factor de riesgo en los DTN. Se analizaron muestras de ADN de 52 madres con antecedente de al menos un hijo con DTN y de 119 madres controles. A través de la reacción en cadena de la polimerasa se amplificó un fragmento de 198 pb, el cual se sometió a digestión con la enzima HinfI. La frecuencia alélica de la MTHFR en los grupos problema y control fue de 51,92% y 34,45%; para el alelo T y 48,08% y 65,55%; para el C respectivamente. Se encontró diferencia significativa entre las frecuencias del alelo T y del alelo C (p: 0,002), así como entre las frecuencias genotípicas (p: 0,007) al ser comparadas en ambos grupos. El odds ratio (OR) para el genotipo TT vs CC se estimó como OR: 4,9 [IC 95%: 1,347-6,416] p: 0,002; CT+TT vs CC: OR: 2,9 [IC 95%: 1,347-6,416] p: 0,005; TT vs CT+CC: OR: 2,675 [IC 95%: 1,111-6,441] p: 0,024. Los presentes datos aportan una asociación significativa entre el polimorfismo 677C>T de la MTHFR y riesgo aumentado en las madres con antecedente de hijos con DTN.

Neural tube defects (NTD) are the most common congenital anomalies of the central nervous system, with a multifactorial pattern of inheritance, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism has been implicated as a risk factor for NTD. The main objective of this research was to investigate the association of the 677C>T polymorphism of the MTHFR gene as a genetic risk factor for NTD. Molecular analysis was performed in DNA samples from 52 mothers with antecedent of NTD offspring and from 119 healthy control mothers. Using the Polymerase Chain Reaction, a 198 bases pairs fragment was digested with the restriction enzyme HinfI. 677T MTHFR allele frequencies for the problem and the control groups were 51.92% and 34.45%, respectively, and 677C MTHFR allele frequencies were 48.08% and 65.55%, respectively. There were significant differences in allele (p: 0.002) and genotype (p: 0.007) frequencies between these two groups. The odds ratio (OR) to the TT genotype vs the CC genotype was estimated as OR: 4.9 [95% CI: 1,347-6.416] p: 0.002; CT+TT vs CC: OR: 2.9 [95% CI: 1.347-6.416] p: 0.005; TT vs CT+CC: OR: 2.675 [95% CI: 1,111-6.441] p: 0.024. The data presented in this study support the relationship between MTHFR 677C>T polymorphism and risk in mothers with antecedent of NTD offspring.

MTHFR Gene (C677t) Polymorphism in Ischemic Stroke, its Subtypes and Hemorrhagic Stroke in a South Indian Population.

Objective: We investigated the association of MTHFR C677T polymorphism with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian Population from Andhra Pradesh. Methods: Six hundred and twenty ischemic stroke patients, 220 hemorrhagic stroke patients and 620 age and sex matched healthy controls, were included in the present study. The polymorphism was determined using PCR-RFLP technique. Results: The strength of association between genotypes and stroke types was measured by the odds ratio with 95% confidence interval and chi-squared analysis. We found significant association of the CT genotype with ischemic stroke as well as haemorrhagic stroke (p<0.05). Further, evaluating the association of this polymorphism with stroke subtypes, we found significant association with intracranial large artery (p<0.05), lacunar stroke (p<0.05) and undetermined etiology (p<0.05). However, there was no significant difference in genotypic or allelic frequencies between ischemic and hemorrhagic strokes. Conclusion: Our study suggests that MTHFR (C677T) is an important risk factor for ischemic stroke, its subtypes and hemorrhagic stroke in the South Indians from Andhra Pradesh but it cannot help in distinguishing between the two types of stroke.

Correlation study of methylenetetrahydrofotate reductase C677T polymorphisms and H-type hypertension and increased homocysteine levels / 中国脑血管病杂志

Objective To investigate the relationship between methylenetetrahydrofotate reductase (MTHFR)C677T polymorphisms and H-type hypertension and increased plasma homocysteine (Hcy) levels. Methods From September 2013 to June 2014,4 012 permanent residents aged ≤30 year from 12 natural villages or communities in 6 regions of Hunan province were extracted according to the cluster random sampling method. Using computer random number table,571 residents were randomly selected as the research objects. According to the blood pressure and Hcy levels,571 residents were divided into 3 groups:a common hypertension group (n = 190),an H-type hypertension group (n = 94),and a normal blood pressure group (n = 287 ). Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR)method was used to detect the MTHFR C677T polymorphisms in all the research objects and the penotyping was performed. Hcy levels were detected at the same time. Results There were significant differences in recessive model (CC + CT,TT)genotype frequencies among the H-type hypertension group (n = 66[70. 2%],n = 28[29. 8%]),common hypertension group (n = 156[82. 1%],n = 34[17. 9%]), and normal blood pressure group (n = 235[81. 9%],n = 52[18. 1%])(χ2 = 6. 797,P = 0. 033),and there were no significant differences in CC,CT,and TT genotype frequencies among the 3 groups (P >0. 05). In the recessive model,there were significant differences in TT genotype frequencies between the H-type hypertension group and the normal blood pressure group or the common hypertension group (χ2 = 5. 812,P = 0. 016;χ2 = 5. 212,P = 0. 022). There was no significant difference in TT genotype frequencies between the common hypertension group and the normal blood pressure group (P > 0. 05). The CC + CT and TT genotype Hcy levels of the MTHFR C677T recessive model in the H-type hypertension group were 17. 1 ±1. 6 and 19. 0 ±2. 9 μmol/ L respectively. There was significant difference between the genotypes (t = - 3. 115,P = 0. 004). The logistic regression analysis of MTHFR C677T recessive model genotype showed that after adjusting for sex and age,the residents with recessive model TT genotype had higher risk of H-type hypertension (OR,1. 946,95% CI 1. 172 -3. 232,P = 0. 01). Conclusion The TT MTHFR C677T gene mutation in this population may be an important genetic factor for the increased Hcy levels and the onset of H-type hypertension.

Comparison of homocysteinemia and MTHFR 677CT polymorphism with Framingham Coronary Heart Risk Score / Comparación de homocisteinemia y polimorfismo 677CT MTHFR con el Escore Framingham de Riesgo Coronario

Objective: The Framingham Coronary Heart Disease Risk Score is an important clinical tool. The aim of this cross-sectional study was to compare plasma homocysteine levels and polymorphism 677CT MTHFR with this score to determine the utility of these new biomarkers in clinical practice. Methods: Plasma homocysteine levels determined by chemiluminescence and polymorphism 677CT MTHFR, detected by PCR-RFLP, were compared with Framingham coronary risk score in a cross-sectional survey on 68 men and 165 women. Results: Coronary heart disease risk augmented with an increase in the quartile of plasma homocysteine. In the 2nd, 3rd and 4th quartile of plasma homocysteine, men showed significantly (P < 0.001) higher risk than women. For the highest quartile of plasma homocysteine, OR of high-risk (10-year risk ≥ 20%) compared with the lowest quartile was 17.45 (95% CI: 5.79-52.01). Frequencies of CT and TT genotype and T allele were not over-represented in the individuals with score ≥ 10%. The higher plasma homocysteine concentrations in individuals with score ≥ 10% with respect to those with low risk (P < 0.005 and P < 0.001) were not due to the presence of T allele. The T allele (CT + TT genotypes) of the MTHFR C677T polymorphism was not significantly associated with an increased risk of coronary disease (OR = 1.09, 95% CI = 0.50-2.39, P = 0.844). Conclusions: The present study demonstrated an association between plasma homocysteine levels and the severity of coronary heart disease estimated with the Framingham coronary risk score, and this association appeared to be independent on the genotype of MTHFR. We postulate that plasma homocysteine is effective enough, considered even in isolation.

Objetivo: La puntuación del riesgo coronario de Framingham es una importante herramienta clínica. El objetivo del presente estudio transversal fue comparar los niveles plasmáticos de homocisteína plasmática y el polimorfismo 677CT de la MTHFR con esta herramienta para determinar la utilidad de estos nuevos biomarcadores en la práctica clínica. Métodos: Los niveles de homocisteína plasmática determinados por quimioluminiscencia y el polimorfismo 677CT MTHFR por PCR-RFLP fueron comparados con la puntuación del riesgo coronario de Framingham en un estudio transversal sobre 68 hombres y 165 mujeres. Resultados: El riesgo de enfermedad coronaria aumentó con el incremento en los cuartiles de homocisteína plasmática. En el segundo, tercero y cuarto cuartil de homocisteína plasmática los hombres mostraron significativamente (p < 0.001) mayor riesgo que las mujeres. Para el cuartil más alto de homocisteína plasmática, la OR de riesgo alto (riesgo a 10 años ≥ 20%) comparado con el cuartil más bajo fue 17,45 (IC 95%: 5,79-52,01; p < 0.001). Las frecuencias de los genotipos CT y TT y del alelo T no estuvieron aumentados en los individuos con una puntuación ≥ 10%. Las mayores concentraciones de homocisteína plasmática en los individuos con una puntuación ≥ 10% respecto a los de bajo riesgo (p < 0.005 y p < 0.001) no se debieron a la presencia del alelo T. El alelo T (genotipos CT + TT) del polimorfismo MTHFR C677T no estuvo significativamente asociado con mayor riesgo de enfermedad coronaria (OR = 1.09, IC 95% = 0.50-2.39, p = 0.844). Conclusiones: El presente estudio mostró una asociación entre los niveles de homocisteína plasmática y la severidad de la enfermedad coronaria estimada con el algoritmo de puntuación de riesgo coronario de Framingham y esta asociación resultó ser independiente del genotipo de MTHFR. Postulamos que la homocisteína plasmática es lo suficientemente eficaz, estudiada incluso aisladamente.

Homocisteína, polimorfismos MTHFR C677T, A1298C y variables clínico-bioquímicas en población mexicana / Homocysteine, MTHFR C677T and A1298C polymorphisms, and clinical and biochemical variables in the mexican population / Homocisteína, polimorfismos MTHFR C677T, A1298C e variáveis clínico-bioquímicas em população mexicana

El objetivo del trabajo consistió en analizar la relación del nivel sérico de homocisteína (Hcy) con los polimorfismos de la metilentetrahidrofolato reductasa MTHFR C677T y A1298C y variables clínicas y bioquímicas en población mexicana. Se determinó el nivel de Hcy (inmunoensayo) y de polimorfismos (PCR/RFLP) en 102 individuos de la población general. El genotipo 677TT mostró asociación significativa con el peso corporal (r=0,012) y el genotipo 1298CC tuvo tendencia a asociarse con el IMC (r~0,06). Los valores séricos de Hcy en mujeres (51/102) fueron 8,33±1,86 µmol/L y en hombres (51/102) 11,64±4,15 µmol/L. La Hcy mostró asociación positiva con peso corporal (r=0,004) y asociación negativa con Hb y Hto (r=0,001). Se encontró mayor nivel de Hcy en individuos fumadores (r=0,009) y una tendencia hacia hiperhomocisteinemia en alcohólicos y en mujeres menopáusicas. No se evidenció asociación de Hcy con los polimorfismos MTHFR C677T y A1298C, sin embargo, el análisis con el modelo de herencia dominante para el polimorfismo C677T (TT+CT vs. CC) mostró un efecto semidominante (r<0,10). En este estudio, la presencia de los polimorfismos MTHFR C677T y A1298C no representó ser un factor de riesgo significativo para hiperhomocisteinemia, sin embargo, se encontraron diferencias que puntualizan la posible dependencia de los niveles de Hcy en relación con los genotipos modificados con diversos factores ambientales.

The objective of the current work was to analyze the relationship of serum homocysteine (Hcy) with MTHFR C677T and A1298C polymorphisms and clinical and biochemical variables in the Mexican population. Hcy (immunoassay) levels and polymorphism (PCR/RFLP) levels were determined in 102 individuals from the general population. The 677TT genotype showed significant association with body weight (r=0.012) and the 1298CC genotype tended to be associated with BMI (r~0.06). Serum levels of Hcy in women (51/102) were 8.33±1.86 µmol/L and in men (51/102) 11.64± 4.15 µmol/L. The Hcy was positively as-sociated with body weight (r=0.004) and negatively with Hb and Hct (r=0.001). Higher levels of Hcy were found in smokers (r=0.009) and a tendency to hyperhomocysteinemia in alcoholics and in menopausal women. There was no association of Hcy with MTHFR C677T and A1298C polymorphisms, although the analysis with dominant inheritance model for the C677T polymorphism (TT + CT vs. CC) showed a semi-dominant effect (r<0.10). In this study, the presence of MTHFR C677T and A1298C polymorphisms did not represent a significant risk factor for hyperhomocysteinemia; however, those differences may point out the dependence of the relative levels of Hcy modifed genotypes on various environmental factors.

O objetivo deste trabalho foi analisar a relação do nível sérico de homocisteína (Hcy) com os polimorfismos da metilenotetrahidrofolato redutase MTHFR C677T e A1298C e variáveis clínicas e bioquímicas na po-pulação mexicana. Foi determinado o nível de Hcy (imunoensaio) e de polimorfismos (PCR/RFLP) em 102 indivíduos da população geral. O genótipo 677TT mostrou associação significativa com o peso corporal (r =0,012) e o genótipo 1298CC teve tendência a se associar com o IMC (r~0,06). Os níveis séricos de Hcy em mulheres (51/102) foram 8,33±1,86 µmol/L e em homens (51/102) 11,64±4,15 µmol/L. A Hcy mos-trou associação positiva com o peso corporal (r=0,004) e associação negativa com Hb e Hto (r=0,001). Encontraram-se níveis mais elevados de Hcy em fumantes (p=0,009) e uma tendência para hiperhomo-cisteinemia em alcoólatras e em mulheres na menopausa. Nenhuma associação se mostrou entre Hcy e os polimorfismos MTHFR C677T e A1298C, no entanto, a análise com modelo de herança dominante para o polimorfismo C677T (TT+CT vs. CC) mostrou um efeito semidominantes (r<0,10). Neste estudo, a presença dos polimorfismos MTHFR C677T e A1298C não representou ser um fator de risco significativo para a hiper-homocisteinemia, no entanto, foram encontradas diferenças que apontam a possível dependência dos níveis de Hcy relativos aos genótipos modificados com diversos fatores ambientais.

Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on the Risk of Lung Cancer and the Clinical Response to Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer: An Updated Meta-Analysis

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) has been implicated in lung cancer risk and response to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the results are controversial. We performed meta-analysis to investigate the effect of MTHFR C677T polymorphism on lung cancer risk and response to platinum-based chemotherapy in advanced NSCLC. MATERIALS AND METHODS: The databases of PubMed, Ovid, Wanfang and Chinese Biomedicine were searched for eligible studies. Nineteen studies on MTHFR C677T polymorphism and lung cancer risk and three articles on C677T polymorphism and response to platinum-based chemotherapy in advanced NSCLC, were identified. RESULTS: The results indicated that the allelic contrast, homozygous contrast and recessive model of the MTHFR C677T polymorphism were associated significantly with increased lung cancer risk. In the subgroup analysis, the C677T polymorphism was significantly correlated with an increased risk of NSCLC, with the exception of the recessive model. The dominant model and the variant T allele showed a significant association with lung cancer susceptibility of ever smokers. Male TT homozygote carriers had a higher susceptibility, but the allelic contrast and homozygote model had a protective effect in females. No relationship was observed for SCLC in any comparison model. In addition, MTHFR 677TT homozygote carriers had a better response to platinum-based chemotherapy in advanced NSCLC in the recessive model. CONCLUSION: The MTHFR C677T polymorphism might be a genetic marker for lung cancer risk or response to platinum-based chemotherapy in advanced NSCLC. However, our results require further verification.

Prevalence of methylenetetrahydrofolate reductase C677T polymorphism in eastern Uttar Pradesh.

AIM: This study was aimed to evaluate the 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation in eastern Uttar Pradesh population. MATERIALS AND METHODS: Polymerase chain reaction (PCR) using specific primers followed by amplicon digestion by Hinf I restriction enzyme was used for MTHFR C677T polymorphism analysis. Total 250 subjects were analyzed. RESULTS: The CC genotype was found in 192 subjects, followed by CT in 56 subjects and TT in 2 subject. Genotype frequencies of CC, CT and TT were 0.768, 0.224 and 0.008, respectively. The frequency of C allele was found to be 0.88 and that of T allele was 0.12. CONCLUSION: It is evident from the results of the present study that the percentage of homozygous genotype (CC) is highest in the target population.

MTHFR C677T Polymorphism, Homocysteine and B-Vitamins Status in a Sample of Chinese and Malay Subjects in Universiti Putra Malaysia

Introduction: Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body. Methodology: This study assessed MTHFR C677T polymorphism and its relationship with serum homocysteine and Bvitamins levels in a sample of Chinese and Malays subjects in UPM, Serdang. One hundred subjects were randomly selected from among the university population. Folate, vitamin B12, B6, and homocysteine levels were determined using MBA, ECLIA, and HPLC, respectively. PCR coupled with HinfI digestion was used for detection of MTHFR C677T polymorphism. Results: The frequency of T allele was higher in the Chinese subjects (0.40) compared to the Malay (0.14). Folate, vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups. Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels. The serum folate and homocysteine were mainly affected by homozygous genotype. Conclusion: MTHFR C677T polymorphism plays an important role in influencing the folate and homocysteine metabolism.