Association of the MTHFR gene polymorphism with non-syndromes cleft lip with or without cleft palate in XinJiang Uyghur and Han population / 实用口腔医学杂志

Objective:To explore the relationship of NSCL/P with MTHFR gene polymorphism in Xinjiang Uyghur and Han popula-tion and the ethnic difference.Methods:rs1801131 and rs1801133 polymorphism was detected by SNaPshot genotype method in 170 children with NSCL/P and 100 healthy controls of Uyghur and Han population.Results:Rs1801133 TT and T allele was statistically difference between 2 nationalities(P 0.05).Conclusion:Rs1801133 TT and T allele in Han nationality are more likely to suffer from NSCL/P than in Uyghur,rs1801133 CT and CT +TT genotypes are protective factors.Rs1801131AC and rs1801133CC conjoint is relevant to NSCL/P,and the risk in Uyghur is higher than in Han.MTHFR rs1801131 gene polymorphism may not be relat-ed with NSCL/P in Uyghur or Han.

ARMS-PCR Based SNP Analysis of MTHFR C677T Allele Using Syber Green in Pancreatic Tumour.

In human, carcinoma of pancreas, a rare disease and mortality rate is quite high in Indian population. Epidemiological studies support the hypothesis that folate metabolism regulate DNA stability and prevent cancer. Because folate have been linked to dietary supplement and defect in folate metabolism have been increase risk of developing cancer shows adverse effect on health conditions. In the present study we have assess methylene tetrahydrofolate reductase gene polymorphism (MTHFR) 677 C → T using ARMS PCR based SNP analysis using Syber green in the cases of pancreatic tumour to determine the “risk factor”. Interestingly, our findings reveals that 33.0% frequency (one case) showing mutation of MTHFR 677 TT genotype (rare type) in homozygous condition with Tm value 82.50°C for mutant 677T allele shifted to 677C allele (83.50°C).Two cases (66%) showing CC (wild type) allele and Tm value 82.83°C for 677C allele. In MTHFR 677TT is a rare mutation and individuals show very low enzymatic activity due to the substitution of alanine to valine. The study further continue to confirm the mutation by visualization on agarose gel electrophoresis of the same PCR product, again showing (Lane- 2) the band of 50 kb of mutant 677TT allele in the same case, suggesting an relevant role of folate metabolism and subsequent impairment of aberrant DNA methylation during carcinogenesis with increasing “high risk” for the development of carcinoma due to allele TT mutation of MTHFR. However, large samples size is required to further confirm the association.

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism and Homocysteine Levels are Risk Factors for Myocardial Infarction.

Increased plasma total homocysteine (tHcy) levels shown to be a risk factor for coronary artery disease (CAD). The common methylenetetrahydrofolate reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation was associated with increased risk of myocardial infarction (MI) and plasma levels of tHcy. The study group consisted of 210 angiographically proven MI patients, and 202 age and sex matched healthy individuals as controls. MTHFR (C677T) gene polymorphism was detected based on the polymerase chain reaction and restriction digestion with HinfI. Total homocysteine plasma concentration was measured using immunoassay. T allele frequency was not found to be significantly higher in patients than in the control group: T vs. C was χ2=0.19, OR 1.0, CI 95% 0.8–1.4, p=0.6; and TT vs. CC was χ2=0.24, OR 1.2, CI 95% 0.6–2.3, p=0.6.We found significantly elevated levels of mean homocysteine in the patient group when compared to the control group (p =0.00). Our findings showed that MTHFR C677T polymorphism is not a risk factor for myocardial infarction in South Indian population and higher levels of homocysteine in patients indicated that the severity of the disease is independent of homocystein levels.

Association of homocysteine and methylene tetrahydrofolate reductase (MTHFR C677T) gene polymorphism with coronary artery disease (CAD) in the population of North India

The implications of the methylene tetrahydrofolate reductase (MTHFR) gene and the level of homocysteine in the pathogenesis of coronary artery disease (CAD) have been extensively studied in various ethnic groups. Our aim was to discover the association of MTHFR (C677T) polymorphism and homocysteine level with CAD in north Indian subjects. The study group consisted of 329 angiographically proven CAD patients, and 331 age and sex matched healthy individuals as controls. MTHFR (C677T) gene polymorphism was detected based on the polymerase chain reaction and restriction digestion with HinfI. Total homocysteine plasma concentration was measured using immunoassay. T allele frequency was found to be significantly higher in patients than in the control group. We found significantly elevated levels of mean homocysteine in the patient group when compared to the control group (p = 0.00). Traditional risk factors such as diabetes, hypertension, smoking habits, a positive family history and lipid profiles (triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol), were found significantly associated through univariate analysis. Furthermore, multivariable logistics regression analysis revealed that CAD is significantly and variably associated with diabetes, hypertension, smoking, triglycerides and HDL-cholesterol. Our findings showed that MTHFR C677T polymorphism and homocysteine levels were associated with coronary artery disease in the selected population.

Clinical Study on Relationship between Polymorphism in Methylenetetrahydrofolate Reductase and Hcy and Acute Cerebral Infarction / 中国康复理论与实践

@#Objective To investigate the relationship between polymorphism in methylenetetra-hydrofolate reductase (MTHFR ) and acute cerebral infarction (CI), observe the variation regular of fasting plasma homocysteine (Hcy) level.Methods Using Homocysteine Microplate STE Assay to examine the fasting plasma homocysteine level of 28 CI patients during their initial stage (flaring up between 1 to 3 days) and later stage (flaring up 10 to 15 days) of acute period and 27 healthy controls. The presence of the MTHFR genetic type was determined by polymerase chain reaction (PCR) assay and subsequent restriction enzyme digestion.Results There was no significant difference among the three MTHFR genotypes in distributed frequency of the CI group, normal controls and the 677 allelic gene (P>0.05). The discrepancy of Hcy level in various kinds of genotypes: heterozygote mutation and homozygoto mutation were much higher than wild type (P<0.01). Homozygoto mutation was higher than heterozygote mutation, but there was no significant difference between them (P>0.05). The high homocysteine of group CI during the acute early stage were found out more frequent than normal control (P<0.05). There was no significant difference of fasting plasma Hcy level between the initial stage and later stage of CI group which were in acute period (P>0.05), both of the Results were higher than normal control (P<0.01). There was no significant difference among the Hcy level of various genetypes in CI group during the initial stage and later stage of acute period (P<0.05).Conclusion MTHFR gene C677T mutation is one of the cause of high homocystinemia, while it dose not lead to CI directly. High Hcy level is the independent risk factor of CI, but has no concern to the course of acute CI.

Polymorphism of the 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Gene and Microsatellite Instability (MSI) in Mucinous Colorectal Cancer

PURPOSE: Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc. METHODS: From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses. RESULTS: MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups. CONCLUSIONS: The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.

The Effect of Folic Acid to the Level of Homocysteine and Analysis of the Factors in Epilepsy Patients / 대한간질학회지

BACKGROUND: Folic acid has been frequently used for hyperhomocyesteinemia in various diseases and decreases the level of homocysteine. OBJECTIVES: To assess the effect of folic acid in the level of homocysteine in epilepsy patients, and to analyze factors affecting its responsiveness and the difference of its efficacy according to methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. METHODS: Total 75 epilepsy patients with antiepileptic drugs (AEDs) therapy were included. 41 patients had normal level of homocysteine and 34 patients with hyperhomocysteinemia (> or =12 micro mol/ ) were supplemented with folic acid for 1 year. Thirty-four patients with hyperhomocyteinemia were divided into two groups according to the responsiveness of homocysteine to folic acid; decrease group (DG) and non-decrease group (NDG). RESULTS: The level of homocysteine in patients with hyperhomocysteinemia was significantly decreased after administration of folic acid, comparing with patients with normal level. DG was younger and had more male gender, shorter duration of seizure, and initial higher homocysteine level, compared to NDG (p<0.05). Patients with mutant type of MTHFR (CT+TT) had more decreased homocysteine level after supplement of folic acid, but had more increased homocysteine level without supplement of folic acid. Comparing between MTHFR genotypes, TT type had the most decreased homocysteine level than others, but there was no significance. CONCLUSION: Folic acid is useful treatment of hyperhomocysteinemia in epilepsy patients and the supplement of folic acid might be considered in patients with mutant type of MTHFR regardless of homocysteine level. The effect of folic acid supplement is greater in younger age, male sex, shorter duration of seizure, and initial higher homocysteine level.

Prevalence of folate deficiency and hyperhomocysteinemia in a developing country: results from a large population study in Venezuela

To evaluate the prevalence of hyperhomocysteinemia in apparently healthy individuals and its relationship to the classical cardiovascular risk factors and nutritional and genetic determinants in a developing country a randomized crosssectional study was made in the Venezuelan population. Apparently healthy subjects (N = 3400; 9 – 60 yr) recruited, on a voluntary basis, from urban and rural areas in 9 states of the country which gather more than 60% of the total population. A Clinical and anthropometric evaluation, fasting plasma glucose, creatinine, blood lipids, fibrinogen, C-reactive protein, plasma total homocysteine (tHcy), folic acid and vitamin B12 were done in all subjects. The C677 --> T polymorphism of MTHFR was evaluated in a random sub-sample of the mixed-blood population (N = 535) and in a sample of Venezuelan blacks (N = 115). Final analysis was done on 3062 subjects (1608 females, 1454 males). An important deficiency in plasma folate was found (~ 50 percent of recommended value), in 86.0 percent of the population. Mean value for tHcy stays below 10.5 μmol/L for both genders in all age ranges studied. Hyperhomocysteinemia (> 12 μm/L) is found in 12 percent of females and 26 percent of males. MTHFR polymorphismreflects the spanish genic penetration. There is no association between hyperhomocysteinemia and the polymorphism. Hyperhomocysteinemia in our population is mainly related to marked deficiency in folic acid. The relatively lower mean values of tHcy, compared to developed countries, seem related to a general nutritional deficit.

La prevalencia de hiperhomocisteinemia y su relación con determinantes genéticos, nutricionales y factoresclásicos de riesgo cardiovascular, fue evaluada a través de un estudio epidemiológico, al azar, de tipo corte transversal, en una muestra razonablemente representativa de la población en Venezuela para el período del estudio. Se evaluaron sujetos aparentemente sanos (n = 3400; de 9 a 60 años de edad), provenientes de áreas rurales y urbanas de 9 estados del país. A todos los sujetos se les realizó una evaluación clínica y antropométrica y se les determinó glucosa sanguínea en ayunas, perfil lipídico, creatinina, fibrinógeno, proteína C reactiva, homocisteína total plasmática (tHcy), ácido fólico, vitamina B12. El polimorfismo MTHFR C677 T fue evaluado en una muestra al azar total de 650 sujetos (Mestizo = 535; Negros = 115). La muestra total analizada fue de 3062 sujetos (Femeninos = 1608; Masculinos = 1454). Se encontró una importante deficiencia de ácido fólico (86% de la población tiene valores cercanos al 50 por ciento del valor de folato recomendado). EL valor promedio de tHcy fue menor de 10,5 μM para ambos sexos en todos los grupos etarios evaluados. La prevalencia de hiperhomocisteinemia (>12 μM) fue de 12 por ciento en mujeres y 26 por ciento en hombres. El polimorfismo MTHFR C677 T, refleja la penetración génica española. La prevalencia de hiperhomocisteinemia en la población venezolana está principalmente relacionada con la deficiencia de ácido fólico.

The Study of 5,10-Methylenetetrahydrofolate Reductase Polymorphism and Its Effect on Pregnancy Outcomes among the Korean Population / 대한주산의학회잡지

OBJECTIVE: The purpose of this study was to analyze MTHFR polymorphism among the Korean population and to evaluate the relationship between serum levels of homocysteine and MTHFR polymorphism and also to investigate the effect on pregnancy outcomes. METHODS: DNA was extracted from whole blood of 600 pregnant women. All samples were genotyped for the C677T and A1298C polymorphisms in MTHFR gene by PCR-RELP assay. Serum levels of homocysteine and folate were measured by high performance liquid chromatography for homocysteine and radioassay for folate. Pregnancy outcomes were estimated by gestational weeks and birth weights of newborns. RESULTS: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR C677T polymorphism (p<0.05). And also serum homocysteine was higher in women with the A/A genotype than those with the A/C or C/C genotype of the MTHFR A1298C polymorphism (p<0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes, especially prominent in T/T genotype of MTHFR C677T polymorphism and A/A genotype of MTHFR A1298C polymorphism. Gestational age and the birth weight of infant from hyperhomocysteinemic mothers whose homocysteine levels higher than 15 micromol/L were 36.1 weeks, 3053.8g, respectively, which were significant lower than those from normohomocysteinemic mothers (38.3 weeks, 3,215.3g) (p<0.05). CONCLUSION: Serum homocysteine was influenced significantly by MTHFR C677T polymorphism and MTHFR A1298C polymorphism. MTHFR C677T and A1298C polymorphism and serum homocysteine levels affect pregnancy outcomes, although not mainly by serum folate level.

THE IMPACTS OF VARIATION OF FOLATE METABOLIC COMPONENT AND MTHFR C677T POLYMORPHISMS ON CHROMOSOME SEGREGATION / 营养学报

Objective To study the impacts of variation of folate metabolic component including folic acid (FA), riboflavin (RF) and MTHFR C677T polymorphism on chromosome 8 and 17 segregation. Method RPMI1640 medium was modified with different combinations of low (LF) and high (HF) concentrations of folic acid (20, 200 nmol/L) and low (LR) and high (HR) concentrations of riboflavin (1 and 500 nmol/L). The lymphocytes with different MTFHR C677T genotype were cultured in the mentioned media for 9d. Cytokinesis was blocked by cytochalasin B and the slide was prepared as usual. The frequencies of aneuploidy of chromosomes 8 and 17 were determined by dual-color fluorescence in situ hybridization (FISH). Results The frequencies of both chromosome aneuploidy were significantly higher in low FA (LFLR+LFHR) than that in higher FA (HFLR+HFHR) (P

THE IMPACTS OF FOLIC ACID, RIBOFLAVIN AND MTHFR C677T POLYMORPHISM ON HUMAN LYMPHOCYTES GENOMIC STABILITY / 营养学报

Objective: To explore the comprehensive effects of folic acid (FA), riboflavin (RF) and MTHFR C677T polymorphism on genomic stability. Method: Cytokinesis-block micronucleus assay was used to detect the effects of different concentration combination of FA (20 and 200nmol/L, i.e. LF and HF) , RF (1 and 500 nmol/L, i.e. LR and HR) and MTHFR C677T polymorphism on genomic stability of 9 d cultured human lymphocytes. Results: The genetic damage was significantly higher in LFHR group regardless the genotype (P

Effects of Maternal Serum B vitamins, Homocysteine Concentrations and the 5, 10-Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism on Pregnancy Outcomes

Maternal nutritional status has been shown to influence pregnancy outcomes. And the elevated maternal plasma homocysteine concentrations have been associated with adverse pregnancy outcomes. We investigated the effects of maternal serum levels of B vitamins and homocysteine, and the C677T MTHFR (5, 10-methylenetetrahydrofolate reductase) polymorphism on pregnancy outcomes. In 177 pregnant women of 24-28 wks of gestation, the MTHFR gene mutation, serum B vitamins and homocysteine concentrations were measured, and their pregnancy outcomes were investigated from medical records. The birth length, and 1- and 5-min Apgar scores of neonates in the T/T mothers were 45.4+/-9.3 cm, 7.6+/-3.2 and 8.5+/-3.8, respectively, which were significantly lower than those in the C/T (48.6+/-3.3 cm, 9.0+/-0.2, 10.0+/-0.2) or the C/C mothers (49.4+/-1.9 cm, 9.0+/-0.2, 10.0+/-0.0). The birth weight, birth length and the gestational age of neonates at delivery from hyperhomocysteinemic mothers whose homocysteine levels higher than 15 micromol were 2.5+/-1.3 kg, 43.9+/-9.0 cm, 35.4+/-6.3 wk, respectively, which were significant lower than those from normohomocysteinemic mothers (3.1+/-0.6 kg, 48.8+/-3.6 cm, 38.5+/-2.5 wk). The birth weight and birth length of neonates in mothers whose PLP levels were below the median were significantly lower than those from mothers with the PLP levels above the median. The 1- and 5-min Apgar scores of neonates were lower in mothers with the T/T MTHFR genotype than those with the C/T or C/C only when the serum PLP levels were below the median. The 1-, 5 min Apgar scores and birth length of neonates were lower in mothers with the T/T MTHFR genotype than those with the C/T or C/C only when the serum FMN levels were below the median. In conclusion, maternal B vitamin status, homocysteine and the C677T MTHFR genotype seem to have played an important role on pregnancy outcomes.