Humans ; Methylenetetrahydrofolate Reductase (NADPH2)/metabolism* ; Genotype ; CRISPR-Cas Systems ; Polymorphism, Genetic ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Gene Frequency

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 (Psychology) ; Female ; Flow Cytometry ; Folic Acid ; Haplotypes ; Humans ; Killer Cells, Natural* ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2) ; Odds Ratio ; Pregnancy*

The folate metabolic pathway plays important roles in cellular physiology by participating in nucleotide synthesis, DNA repair and methylation, and maintenance and stability of the genome. Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme involved in folate metabolism. Polymorphisms of MTHFR may change the level of homocysteine and affect DNA synthesis and methylation, leading to an increased oxidative stress and disturbed methylation reactions and consequently affecting reproductive function. This article presents an overview on MTHFR gene polymorphisms, proposing that multicentered, large-sample and long-term prospective studies are needed to reveal the relationship between MTHFR gene polymorphisms and infertility.
DNA ; biosynthesis ; DNA Methylation ; DNA Repair ; Folic Acid ; metabolism ; Homocysteine ; metabolism ; Humans ; Infertility ; enzymology ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic ; Prospective Studies

Acute mesenteric venous thrombosis (MVT) is an uncommon form of intestinal ischemia with high mortality and usually occurs in the setting of preexisting comorbidities including thrombophilia and abdominal inflammatory conditions. Hyperhomocysteinemia has been known to be a risk factor for thromboembolism, often located on an unusual site. Considering that homocysteine metabolism is determined genetically to a high degree, a mutant of methylenetetrahydrofolate reductase (MTHFR) C677T causes hyperhomocysteinemia, leading to thrombophilia. Until now, there have been few reports of MVT associated with MTHFR gene mutation. We, herein, report a case of small bowel infarction associated with MVT by MTHFR gene mutation in an adult without any other risk factors of thrombophilia.
Adult ; Comorbidity ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Infarction* ; Ischemia ; Mesenteric Veins ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Mortality ; Risk Factors ; Thromboembolism ; Thrombophilia ; Thrombosis ; Venous Thrombosis*

PURPOSE: Hyperhomocysteinemia has been identified as an independent risk factor in arterial and venous thrombosis. Mutations in genes encoding methylenetetrahydrofolate reductase (MTHFR), involved in the metabolism of homocysteine, may account for reduced enzyme activity and elevated plasma homocysteine levels. In this study, we investigated the interrelation of MTHFR C677T genotype and level of homocysteine in patients with arterial and venous thrombosis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 146 patients who were diagnosed as having arterial and venous thrombosis. We excluded patients diagnosed with atrial fibrillation. We examined routinely the plasma concentration of total homocysteine level and MTHFR C677T polymorphism for evaluation of thrombotic tendency in all patients. Screening processes of MTHFR C677T polymorphism were performed by real-time polymerase chain reaction. RESULTS: Investigated groups consisted of thrombotic arterial occlusion in 48 patients and venous occlusion in 63 patients. The distribution of the three genotypes was as follows: homozygous normal (CC) genotype in 29 (26.1%), heterozygous (CT) genotype in 57 (51.4%), and homozygous mutant (TT) genotype in 25 (22.5%) patients. There were no significant differences among individuals between each genotype group for baseline characteristics. Plasma concentration of homocysteine in patients with the TT genotype was significantly increased compared to the CC genotype (P<0.05). CONCLUSION: We observed a significant interaction between TT genotypes and homocysteine levels in our results. The results might reflect the complex interaction between candidate genes and external factors responsible for thrombosis.
Atrial Fibrillation ; Genotype ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Mass Screening ; Medical Records ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Plasma* ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Risk Factors ; Thrombosis ; Venous Thrombosis

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.
Atherosclerosis ; Dementia ; DNA ; Eclampsia ; Epilepsy ; Female ; Folic Acid ; Homocysteine ; Hyperhomocysteinemia* ; Metabolism ; Methionine ; Methylation ; Methylenetetrahydrofolate Reductase (NADPH2) ; Multiple Sclerosis ; Myocardial Infarction ; Nervous System ; Nervous System Diseases* ; Parkinson Disease ; Plasma ; Pregnancy ; Stroke ; Vitamin B 12 ; Vitamins

Animals ; Cardiovascular Diseases ; etiology ; Cerebrovascular Disorders ; etiology ; Homocysteine ; metabolism ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic

Child, Preschool ; Cystathionine beta-Synthase ; genetics ; Folic Acid ; blood ; metabolism ; Genetic Predisposition to Disease ; Heart Defects, Congenital ; enzymology ; genetics ; Humans ; Infant ; Infant, Newborn ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Methyltransferases ; genetics ; Minor Histocompatibility Antigens ; Polymorphism, Genetic ; Risk Factors

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) is the main regulatory enzyme for homocysteine metabolism. In the present study, we evaluated whether the MTHFR 677C>T and 1298A>C gene polymorphisms are associated with SBI and plasma homocysteine concentration in a Korean population. MATERIALS AND METHODS: We enrolled 264 patients with SBI and 234 healthy controls in South Korea. Fasting plasma total homocysteine (tHcy) concentrations were measured, and genotype analysis of the MTHFR gene was carried out. RESULTS: The plasma tHcy levels were significantly higher in patients with SBI than in healthy controls. Despite a significant association between the MTHFR 677TT genotype and hyperhomocysteinemia, the MTHFR 677C>T genotypes did not appear to influence susceptibility to SBI. However, odds ratios of the 1298AC and 1298AC + CC genotypes for the 1298AA genotype were significantly different between SBI patients and normal controls. The frequencies of 677C-1298A and 677C-1298C haplotypes were significantly higher in the SBI group than in the control group. CONCLUSION: This study demonstrates that the MTHFR 1298A>C polymorphism is a risk factor for SBI in a Korean population. The genotypes of 677C>T and 1298A>C polymorphisms interact additively, and increase the risk of SBI in Korean subjects.
Aged ; Asian Continental Ancestry Group ; Brain Infarction/*genetics/*metabolism ; Female ; Genotype ; Haplotypes ; Homocysteine/*metabolism ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Polymorphism, Genetic/*genetics

OBJECTIVETo investigate the correlationship between congenital heart disease and 5, 10-methylenetetra hydrofolate reductase (MTHFR)'s C677T or folacin intakes, and to study the interaction of them in the occurring of congenital heart disease.

METHODSWe used case-control study (case = 104, control = 208) method. Cases and controls were chosen by age, sex and other conditions. The MTHFR C677T genotype distribution was analyzed by using polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP), and non-conditional and multi-conditional logistic regression analysis were also used to analyze the correlationship and interaction of the factors.

RESULTSIn case group, the number of people in low folacin intake level was 38 (36.54%), which in control group was 21(10.10%). The intake level of folacin during pregnancy was related to congenital heart disease (chi(2) = 31.614, nu = 1, P < 0.0001). The value of OR was 1.417 with 95%CI 1.216 - 1.651, indicating that the low level of folacin intakes was a risk factor to the congenital heart disease. In case group, the number of TT genotype was 46 (44.24%), the number of CT genotype was 42 (40.38%), the number of CC genotype was 16 (15.38%). In control group, the number of TT genotype was 39 (18.75%), the number of CT genotype was 114 (54.81%), the number of CC genotype was 55 (26.44%). A significant genotype distribution difference was identified between case and control group (chi(2) = 23.13, nu = 2, P < 0.0001). Genotype MTHFR 677TT was a risk factor of congenital heart disease and the OR value was 3.437 (95%CI: 2.042 - 5.784). The interaction analysis suggested that the low level of folacin intakes and the MTHFR 677TT genotype had a positive adding effect in the occurring of congenital heart disease. After adjusted some factors such as the ages of parents, fetus age and sex, the effect values of interaction were 13.343 and 15.911 respectively, and the percentages of attributable interaction effects were 0.619 and 0.612. The percentages of effect values of interaction between pure factors were 0.649 and 0.637 and the population attributable risks were 25.26% and 27.82% according to the estimated exposure rate of population risk factors.

CONCLUSIONThe low level of folacin intakes during pregancy should be a risk factor to congenital heart disease and the MTHFR 677TT genotype be correlated to congenital heart disease. There is interaction between folacin intakes and the MTHFR 677TT genotype. Increasing the intakes of folacin among MTHFR 677TT genotype people might decrease the incidence rate of congenital heart disease.

Case-Control Studies ; Child, Preschool ; Female ; Folic Acid ; metabolism ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Heart Defects, Congenital ; genetics ; metabolism ; Humans ; Infant ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Pregnancy ; Risk Factors