The mthfr gene produces an enzyme called methylenetetrahydrofolate reductase. Investigation of mthfr gene c677t polymorphism in cardiac. The results showed that mthfr c677t polymorphism may be a risk factor for ad in asians, apoe. The two mthfr gene polymorphisms that are the most common and the most frequently studied are 677ct and a change that replaces the nucleotide adenosine with the nucleotide cytosine at position 1298 written. Research indicates that individuals who have the 677ct polymorphism on both copies of the mthfr gene have an increased risk of developing vascular disease, including heart disease and stroke. With the identification of additional patients with severe mthfr deficiency, the heterogeneity of this disorder became manifest. However, having a common variant in the mthfr gene does not change your medical care. Molecular biology of methylenetetrahydrofolate reductase mthfr and overview of mutationspolymorphisms daniel leclerc, sahar sibani and rima rozen assays for methylenetetrahydrofolate reductase polymorphisms arve ulvik and per magne ueland biochemical characterization of. Mthfr c677t is a common gene polymorphism that has been shown to be associated with hyperhomocysteinemia. Mthfr c677t polymorphism rs18013 was examined by polymerase chain reaction pcrrestriction fragment length polymorphism rflp.
The link between mthfr gene mutations and disease, including thyroid health an interview with dr. Mthfr, cancer, c677t, a1298c, and polymorphisms were key words used to focus the search. Mthfr gene variant genetic and rare diseases information. Methylenetetrahydrofolate reductase mthfr is a critical enzyme in both folate and homocysteine metabolism. Abstract studies of genetic polymorphisms associated with the diseases of opiate dependency and abuse have focused primarily on genes related to dopamine and opioid receptors, neurotrophic factors, or the catecholomethyltransferase comt gene 1,2. Mthfr 101 is a guide designed to remove the frustrating research and confusion that comes with this genetic variation. Genotype distributions of the mthfr c677t and nnmt rs694539 polymorphisms were similar in the two groups when evaluated separately and also according to the dominant genetic model p0. Jan, 2016 there are over fifty types of mthfr gene mutations. Learn about determining your mthfr status and getting treatment. In other words, the likelihood of having one or both of the mthfr polymorphisms, as well as the frequency of variants alleles of the mthfr gene, were not found to be more prevalent in those with autoimmune thyroid disease compared to those who do not. Disease associations with the mthfr c677t polymorphism associated with the following disease states. The 677t variant of the methylenetetrahydrofolate reductase gene mthfr has been identified as a risk factor for vascular disease. Subgroup and sensitivity analysis results showed that this polymorphism is a risk factor for down syndrome pregnancy in asian populations but not in caucasian population as well as in overall metaanalysis.
To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly mtrr a66g, rfc1 g80a, and mthfr c677t and a1298c, and disease activity in mexican patients with rheumatoid arthritis ra treated with methotrexate mtx. Thats an increase of 2,637 papers in 7 years at a rate of 376 new papers published a year. Cancer neural tube defects male infertility miscarriages diabetic nephropathy stroke schizophrenia, anxiety, depression, dementia selhub j. Up to 50% of people carry a genetic variation or snp pronounced snip of the mthfr gene. The 677ct polymorphism of mthfr was investigated in the analysis of ioannidis et al. To date, there have been some casecontrol studies of mthfr functional polymorphisms in autism and asd 14, 15, 17. The issue of a gene called mthfr and its link to disease includingthyroid disease is becoming an. It is the gene responsible for facilitating methylation, repairing dna, protein formation, homocysteine conversion, folate processing, and toxin detoxification. Molecular biology of methylenetetrahydrofolate reductase.
Mthfr which is the abbreviation for the gene called methylenetetrahydrofolate reductase, i turned to dr. The aim of the present study was to assess the risk of mthfr c677t polymorphism for ad. Im currently writing a book on the most effective naturopathic treatments for mental health disorders such as anxiety and depression and will be including a chapter on mthfr in this book. This book covers many of the complex traits that have been reported to be influenced by the wellcharacterized 677ct variant. Disease associations with the mthfr a1298c polymorphism associated with the following disease states. Mthfr gene polymorphism positive treatmentresistant. Mthfr mutation may increase the risk of cardiovascular disease and vitamin b deficiencies those with an mthfr mutation are at risk for poor mthfr enzyme efficiency. The authors of this book examine the importance of mthfr in health and disease, including the folate requirements in healthy young women and its potential health implications and the role folate deficiency and mthfr polymorphisms may play in the complex mechanism of global dna hypomethylation. For the 677t polymorphism, homozygote variants have 30% enzyme activity in comparison with homozygotes for the wildtype 677c allele, while heterozygotes retain 65% wildtype mthfr enzyme activity 8, 16. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. The association between methylenetetrahydrofolate reductase mthfr c677t polymorphism and susceptibility to alzheimers disease ad was examined in previous studies. Methylenetetrahydrofolate reductase mthfr is key enzyme of folatehomocysteine pathway. A maternal mthfr a1298c polymorphism is associated with down syndrome pregnancy. However, the two that are most commonly studied and tested for are c677t and a1298c.
I was just diagnosed and had no idea what i was dealing with or where to find information. The mthfr c677t polymorphism contributes to increased risk of. The methylenetetrahydrofolate reductase mthfr gene 677c t polymorphism was reported to be related to an elevated level of homocysteine hcy which is an independent factor for coronary heart disease and stroke. Mthfr polymorphisms, and thus lowered lmethylfolate levels is associated with symptoms and conditions such as mental health disorders, cardiovascular disease, obesity and birth defects. Mthfr is a gene that makes an enzyme called m ethylene t etra h ydro f olate r eductase. Blom neuropsychiatric disease and methylenetetrahydrofolate reductase b.
Other papers discuss the relationship of mthfr polymorphisms to arterial occlusive disease, venous thrombosis, neural tube defects, pregnancy complications, neuropsychiatric disease, renal failure, colorectal neoplasia, and pharmacogenetics. Oct 21, 20 the 1298ac polymorphism in methylenetetrahydrofolate reductase mthfr. Because each person has two copies of the mthfr gene, people can inherit one copy of a mthfr gene variant or two copies of it one from each parent. Since then, more than 5,000 studies have tried to link mthfr variants to a terrifying grab bag of more than 400 health problems. Mthfr gene, folic acid, and preventing neural tube defects. The mthfr c677t polymorphism causes thermolability and reduced mthfr activity, leading to lower levels of 5methyltetrahydrofolate, an accumulation of 5,10methylene thg, increased plasma homocysteine levels and change in the cellular composition. Theres a decent chance you or someone in your family has the mthfr gene variant.
Jan 27, 2012 mthfr research is growing at an exponential rate. Mthfr polymorphisms and cardiovascular disease mthfrsupport. A gene variant is a change in a dna sequence that is different from the expected dna sequence. When we identify a part of the sequence that varies, we call it a variant. Mthfr gene c677t polymorphism in autism spectrum disorders. Mthfr polymorphisms our genes have a significant influence over our health and they may have variations, called single nucleotide polymorphisms snps, affecting the way we process nutrients or our dietary requirements. Folate, vitamin b12, homocysteine, and the mthfr 677ct polymorphism in anxiety and depressionthe hordaland homocysteine study. Some mutations of the mthfr gene may be associated with health problems and complications in pregnancy. Cardiovascular disease renal failure congenital abnormalities and pregnancy outcome cancer psychiatric disorders, schizophrenia, dementia, depression ibd autism downs syndrome.
I have a list of resources on the mthfr page that you might find helpful. One mutation is known as the c677t polymorphism and is far more prevalent in. Methylenetetrahydrofolate reductase mthfr in health and. They found that the frequencies of the genetic marker of interest in control populations often 58% showed large. The most common variant in the mthfr gene is mthfr c677t. A modest positive association has been found between the mthfr thermolabile polymorphism and many different medical complications, including, but not limited to, thromboembolic disease in. The methylenetetrahydrofolate reductase mthfr c677t polymorphism is associated with various diseases vascular, cancers, neurology, diabetes, psoriasis, etc with the epidemiology of the polymorphism of the c677t that varies dependent on the geography and ethnicity. Jun 18, 2012 in particular, the c677t polymorphism shows a wide regional and ethnic variation. A recent, huge metaanalysis was designed to investigate the association of mthfr c677t polymorphism with ad.
Ben lynch, expert on mthfr polymorphisms by mary shomon updated june, 2014. Methylene tetrahydrofolate reductase mthfr is an important enzyme in the mtx pathway and is involved in folate metabolism and dna synthesis. Pdf preface of book mthfr polymorphisms and disease. Association of mthfr a1298c polymorphism with conotruncal. Our results suggest that mthfr 1298c allele is a risk factor for conotruncal heart disease. Mthfr gene polymorphism, homocysteine and cardiovascular disease claudio cortese1 and corradino motti2 1department of internal medicine, university of tor vergata, via di tor vergata 5, 003 rome, italy.
Natural variation in this gene is common in otherwise healthy people. It lists the main functional polymorphisms of the mthfr gene to be c677t, a1298c, with other reported polymorphisms known for genes t1059c, t17c and g1793a. Polymorphisms in the mthfr gene can alter or decrease the activity of methylenetetrahydrofolate reductase, leading to a mild increase of homocysteine in the blood hyperhomocysteinemia. The 677ct polymorphism has also been suggested as a risk factor for cleft lip and palate, a birth defect in which there is a split in the upper lip and. Studies on the role of mthfr in inflammatory bowel diseases ibd have yielded conflicting results, perhaps due in part to genetic heterogeneity. Consequently, folate and folic acid cannot be efficiently converted into their active form, known as 5mthf or lmethylfolate. Nonetheless, the mthfr gene variation does appear more commonly in those with hypothyroidism. If you have a mthfr gene polymorphism you may not be able to convert folic acid and other inactive forms of folate into the active form that our body needs. Due to various complications, she just started getting breast milk.
You may have an increased risk of heart disease, general inflammation, difficult pregnancies and a diminished ability to eliminate toxins including alcohol. Learn how most of the us population carries the gene for this mysterious disorder mthfr and up to 15% actually have the disease they have methylation problems, folate deficiency, and lack of methylfolate in their diet and its killing them, and possibly. Mthfr is a key gene in regulating the bodys folate metabolism and, consequently, is involved in the methylation cycle. Mthfr polymorphisms and disease by per magne ueland. The mutation of the mthfr gene is a single nucleotide polymorphism that causes an alaninetovaline amino acid substitution 8,15. This means at the 677 position in the mthfr gene, c is the expected dna base and t is the gene variant. If you have an mthfr polymorphism, enzymatic reactions can slow down by 4070%, leading to elevated homocysteine levels. Currently, there are 7215 research articles on mthfr as of june 25, 2019. Mthfr is the gene responsible for production of the mthfr enzyme, which is the ratelimiting enzyme in folate cycle.
Metabolism, genes, polymorphisms and the associated. A primer on methylation beyond mthfr optimizing genes. Several studies have examined the association between the mthfr c677t polymorphism and mtx toxicity and efficacy in ra, but their conclusions remain controversial. Methylenetetrahydrofolate reductase mthfr atp science. Despite the high prevalence of methylene tetrahydrofolate reductase mthfr polymorphisms in numerous neuropsychiatric and. Genetic testing can ascertain whether an individual has one of the common polymorphisms which leads to methylfolate deficiency, and can verify when. She had heart surgery on day 2, and were still in the hospital working on getting home. Sixtyeight patients with ra were included in the study. Case control association studies on mthfr c677t polymorphism and alzheimers disease ad have been repeatedly performed over the last two decades, but the results are inconclusive. There are two primary mthfr mutations, which can be thought of as irregular or incomplete versions of this gene, which later affects the mthfr enzyme introduced above. Nov 30, 2018 the mthfr a1298c polymorphism reduces mthfr enzyme activity to a lesser extent than the mthfr c677t polymorphism.
The association between the c677t polymorphism in mthfr gene and the risk of thyroid cancer. Basic information about the mthfr gene most mthfr testing is unnecessary. Mthfr c677t and a1298c polymorphisms may contribute to the risk of parkinsons disease. Pcr fragments were amplified from 20 ng of each dna sample in 50. Associations of the mthfr rs18013 polymorphism with coronary artery disease and lipid levels. Mthfr c677t and a1298c are the two main polymorphisms that you will read about online and in research studies. Our 4 week old daughter was diagnosed en utero with a congenital heart defect and then 22q after amniocentesis. Mthfr enzyme is responsible for converting 5,10 methylenetetrahydrofolate to 5methyltetrahydrofolate. Neural tube defects, other congenital malformations and single nucleotide polymorphisms in the 5,10 methylenetetrahydrofolate reductase mthfr gene. Of particular relevance to the comments below was the report of a heatsensitive mthfr in some homocystinuric patients, which was assumed to be caused by a deleterious mutation. The mthfr c677t polymorphism was significantly associated with 42 clinical disorders p, mostly relating to the diseases of circulatory system, birth defects, and cancers. Many people have one or two genetic variants in the mthfr gene.
Some polymorphisms on the mthfr gene cause inactivation of the mthfr enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are important risk factor for cardiovascular and cerebrovascular diseases. When methylfolate levels are low, so are neurotransmitters. The mthfr gene is on the short arm of chromosome 1 at location 36. The link between mthfr gene mutations and disease, including. Mthfr tells our body how to create an enzyme involved in breaking down the amino acid homocysteine. I am looking forward to sharing my knowledge that will be based on many years of clinical experience and years of research in this field of health. Higher incidence of c677t polymorphism of the mthfr gene in north indian patients with vascular disease.
Abstract the association between methylenetetrahydrofolate reductase mthfr gene c677t polymorphism and alzheimers disease ad risk has been widely reported with inconsistent results. As a major gene associated with homocysteine levels and various thromboses, it is the gene. Mthfr normally plays a critical role in many important processes throughout the body. In particular, the c677t polymorphism shows a wide regional and ethnic variation.
Methylenetetrahydrofolate reductase and psychiatric diseases. Mutation, polymorphism, variant and sequence changethese terms are used interchangeably throughout the book to denote. Sep 27, 2017 methylenetetrahydrofolate reductase mthfr c677t polymorphism. Mthfr polymorphisms affect the metabolism of folate and may predispose these individuals to a variety of nutrient deficiencies. Methylenetetrahydrofolate reductase mthfr is a key enzyme for the critical process of onecarbon metabolism involving folate and homocysteine metabolisms.
The link between mthfr polymorphisms and cardiovascular disease has been known for some time, however recent research confirms increased risk of depression, bipolar and schizophrenia. Mthfr gene polymorphism, homocysteine and cardiovascular disease. Ben lynch, anaturopathic physician who has focused attention on mthfr polymorphisms and genetic changes, and the linkage to diseases and conditions. Methylenetetrahydrofolate reductase mthfr c677t polymorphism. There are over fifty types of mthfr gene mutations. Bhargava s, ali a, parakh r, saxena r, srivastava lm. Having two c677t variants and elevated homocysteine levels may cause a slightly higher risk for blood clots. Mthfr helps converts folate into the active form methyfolate that the body can use. The c677t methylenetetrahydrofolate reductase mthfr polymorphism affects the distribution between folate species used for dna and rna syntheses and the 5methyltetrahydrofolate form required for homocysteine remethylation and thereby protein synthesis. Mthfr gene mutations are linked to many diseases to varying degrees, including heart disease, birth defects, alzheimers, cancer, and hypothyroidism. Most of these studies have been performed in countries in which subjects are predominantly of white european descent. In regards to the c677t mutation, the heterozygous c677t mutation functions at 65% activity, with. Ben lynch, expert on mthfr gene mutations and polymorphisms.
112 947 599 951 728 407 928 1164 39 298 799 728 1257 1062 104 655 305 693 505 442 1333 1495 1437 1226 1465 690 537 877 968 87 943 1055 168 857 119 290 722 553 137 854 1033 175 46 304