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. The issue of a gene called mthfr and its link to disease includingthyroid disease is becoming an. Methylene tetrahydrofolate reductase mthfr is an important enzyme in the mtx pathway and is involved in folate metabolism and dna synthesis. 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. Investigation of mthfr gene c677t polymorphism in cardiac. Methylenetetrahydrofolate reductase mthfr is key enzyme of folatehomocysteine pathway. Natural variation in this gene is common in otherwise healthy people. This means at the 677 position in the mthfr gene, c is the expected dna base and t is the gene variant. 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. Blom neuropsychiatric disease and methylenetetrahydrofolate reductase b. The mthfr c677t polymorphism contributes to increased risk of. Mthfr normally plays a critical role in many important processes throughout the body. 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.
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. 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. 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. Since then, more than 5,000 studies have tried to link mthfr variants to a terrifying grab bag of more than 400 health problems. The association of the mthfr c677t polymorphism with. The association between the c677t polymorphism in mthfr gene and the risk of thyroid cancer. The 677ct polymorphism of mthfr was investigated in the analysis of ioannidis et al. Consequently, folate and folic acid cannot be efficiently converted into their active form, known as 5mthf or lmethylfolate. 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. Mthfr 101 is a guide designed to remove the frustrating research and confusion that comes with this genetic variation.
Ben lynch, expert on mthfr polymorphisms by mary shomon updated june, 2014. Cancer neural tube defects male infertility miscarriages diabetic nephropathy stroke schizophrenia, anxiety, depression, dementia selhub j. 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. However, having a common variant in the mthfr gene does not change your medical care. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10methylenetetrahydrofolate to 5methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Mthfr c677t and a1298c are the two main polymorphisms that you will read about online and in research studies. 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.
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. 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. Mthfr c677t polymorphism rs18013 was examined by polymerase chain reaction pcrrestriction fragment length polymorphism rflp. When we identify a part of the sequence that varies, we call it a variant. 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. Abstract the association between methylenetetrahydrofolate reductase mthfr gene c677t polymorphism and alzheimers disease ad risk has been widely reported with inconsistent results. Mthfr is a gene that makes an enzyme called m ethylene t etra h ydro f olate r eductase. Metabolism, genes, polymorphisms and the associated.
I have a list of resources on the mthfr page that you might find helpful. Our results suggest that mthfr 1298c allele is a risk factor for conotruncal heart disease. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. Association of mthfr a1298c polymorphism with conotruncal. Neural tube defects, other congenital malformations and single nucleotide polymorphisms in the 5,10 methylenetetrahydrofolate reductase mthfr gene. 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. The results showed that mthfr c677t polymorphism may be a risk factor for ad in asians, apoe. You may have an increased risk of heart disease, general inflammation, difficult pregnancies and a diminished ability to eliminate toxins including alcohol. Mthfr gene polymorphism, homocysteine and cardiovascular disease. The link between mthfr gene mutations and disease, including thyroid health an interview with dr. Thats an increase of 2,637 papers in 7 years at a rate of 376 new papers published a year. Sep 27, 2017 methylenetetrahydrofolate reductase mthfr c677t polymorphism. Jan 27, 2012 mthfr research is growing at an exponential rate. Mthfr c677t is a common gene polymorphism that has been shown to be associated with hyperhomocysteinemia.
With the identification of additional patients with severe mthfr deficiency, the heterogeneity of this disorder became manifest. 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. One mutation is known as the c677t polymorphism and is far more prevalent in. Mthfr gene variant genetic and rare diseases information. Due to various complications, she just started getting breast milk. Methylenetetrahydrofolate reductase and psychiatric diseases. Mthfr gene, folic acid, and preventing neural tube defects. Mthfr gene polymorphism positive treatmentresistant. Mutation, polymorphism, variant and sequence changethese terms are used interchangeably throughout the book to denote.
Mthfr which is the abbreviation for the gene called methylenetetrahydrofolate reductase, i turned to dr. 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. Mthfr polymorphisms and cardiovascular disease mthfrsupport. Mthfr polymorphisms and disease by per magne ueland. A recent, huge metaanalysis was designed to investigate the association of mthfr c677t polymorphism with ad. The 677t variant of the methylenetetrahydrofolate reductase gene mthfr has been identified as a risk factor for vascular disease. The most common variant in the mthfr gene is mthfr c677t. To date, there have been some casecontrol studies of mthfr functional polymorphisms in autism and asd 14, 15, 17.
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. The mutation of the mthfr gene is a single nucleotide polymorphism that causes an alaninetovaline amino acid substitution 8,15. Oct 21, 20 the 1298ac polymorphism in methylenetetrahydrofolate reductase mthfr. Methylenetetrahydrofolate reductase mthfr atp science. Mthfr helps converts folate into the active form methyfolate that the body can use.
I was just diagnosed and had no idea what i was dealing with or where to find information. Methylenetetrahydrofolate reductase mthfr in health and. When methylfolate levels are low, so are neurotransmitters. Theres a decent chance you or someone in your family has the mthfr gene variant.
The mthfr gene produces an enzyme called methylenetetrahydrofolate reductase. Despite the high prevalence of methylene tetrahydrofolate reductase mthfr polymorphisms in numerous neuropsychiatric and. The aim of the present study was to assess the risk of mthfr c677t polymorphism for ad. Mthfr gene c677t polymorphism in autism spectrum disorders. Nov 06, 2014 c677t polymorphism in the mthfr gene a222v, rs18013 is associated with a decrease in enzymatic activity to 3570% in homozygotes. Bhargava s, ali a, parakh r, saxena r, srivastava lm. 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. Pcr fragments were amplified from 20 ng of each dna sample in 50. Mthfr gene mutations are linked to many diseases to varying degrees, including heart disease, birth defects, alzheimers, cancer, and hypothyroidism. Up to 50% of people carry a genetic variation or snp pronounced snip of the mthfr gene. Cardiovascular disease renal failure congenital abnormalities and pregnancy outcome cancer psychiatric disorders, schizophrenia, dementia, depression ibd autism downs syndrome. There are over fifty types of mthfr gene mutations. Methylenetetrahydrofolate reductase mthfr is a critical enzyme in both folate and homocysteine metabolism. Mthfr enzyme is responsible for converting 5,10 methylenetetrahydrofolate to 5methyltetrahydrofolate.
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. The mthfr c677t polymorphism was significantly associated with 42 clinical disorders p, mostly relating to the diseases of circulatory system, birth defects, and cancers. Mthfr, cancer, c677t, a1298c, and polymorphisms were key words used to focus the search. Folate, vitamin b12, homocysteine, and the mthfr 677ct polymorphism in anxiety and depressionthe hordaland homocysteine study. Mthfr c677t and a1298c polymorphisms were associated with bladder cancer risk and disease progression.
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. 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 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. Studies on the role of mthfr in inflammatory bowel diseases ibd have yielded conflicting results, perhaps due in part to genetic heterogeneity. Learn about determining your mthfr status and getting treatment. A maternal mthfr a1298c polymorphism is associated with down syndrome pregnancy. A gene variant is a change in a dna sequence that is different from the expected dna sequence. Genetic testing can ascertain whether an individual has one of the common polymorphisms which leads to methylfolate deficiency, and can verify when. As a major gene associated with homocysteine levels and various thromboses, it is the gene. Mthfr polymorphisms, and thus lowered lmethylfolate levels is associated with symptoms and conditions such as mental health disorders, cardiovascular disease, obesity and birth defects.
This book covers many of the complex traits that have been reported to be influenced by the wellcharacterized 677ct variant. However, the two that are most commonly studied and tested for are c677t and a1298c. Mthfr is the gene responsible for production of the mthfr enzyme, which is the ratelimiting enzyme in folate cycle. Pdf preface of book mthfr polymorphisms and disease. People who inherit two copies of c677t have a higher risk for having a child with a neural tube defect. Many people have one or two genetic variants in the mthfr gene. Nonetheless, the mthfr gene variation does appear more commonly in those with hypothyroidism. Disease associations with the mthfr c677t polymorphism associated with the following disease states. Basic information about the mthfr gene most mthfr testing is unnecessary. Disease associations with the mthfr a1298c polymorphism associated with the following disease states. Molecular biology of methylenetetrahydrofolate reductase. Methylenetetrahydrofolate reductase mthfr c677t polymorphism.
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. She had heart surgery on day 2, and were still in the hospital working on getting home. 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. Associations of the mthfr rs18013 polymorphism with coronary artery disease and lipid levels. Having two c677t variants and elevated homocysteine levels may cause a slightly higher risk for blood clots. 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. Mthfr is a key gene in regulating the bodys folate metabolism and, consequently, is involved in the methylation cycle. 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. Methylene tetrahydrofolate reductase mthfr is the ratelimiting enzyme in the methyl cycle, and it is encoded by the mthfr gene. 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. Sixtyeight patients with ra were included in the study. 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.
The association between methylenetetrahydrofolate reductase mthfr c677t polymorphism and susceptibility to alzheimers disease ad was examined in previous studies. Our 4 week old daughter was diagnosed en utero with a congenital heart defect and then 22q after amniocentesis. Aug 07, 2017 mthfr polymorphisms are also strongly linked to autoimmune disease, specifically type 1 diabetes, hashimotos thyroiditis, graves disease, rheumatoid arthritis, vitiligo, and multiple sclerosis. The link between mthfr gene mutations and disease, including.
Several studies have examined the association between the mthfr c677t polymorphism and mtx toxicity and efficacy in ra, but their conclusions remain controversial. A primer on methylation beyond mthfr optimizing genes. Mthfr polymorphisms affect the metabolism of folate and may predispose these individuals to a variety of nutrient deficiencies. In regards to the c677t mutation, the heterozygous c677t mutation functions at 65% activity, with. They found that the frequencies of the genetic marker of interest in control populations often 58% showed large. 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. Higher incidence of c677t polymorphism of the mthfr gene in north indian patients with vascular disease. It is the gene responsible for facilitating methylation, repairing dna, protein formation, homocysteine conversion, folate processing, and toxin detoxification. 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. Methylenetetrahydrofolate reductase mthfr is a key enzyme for the critical process of onecarbon metabolism involving folate and homocysteine metabolisms. Mthfr polymorphisms and disease by ueland, per magne ebook. Currently, there are 7215 research articles on mthfr as of june 25, 2019.
In particular, the c677t polymorphism shows a wide regional and ethnic variation. 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. Mthfr tells our body how to create an enzyme involved in breaking down the amino acid homocysteine. Ben lynch, expert on mthfr gene mutations and polymorphisms. Most of these studies have been performed in countries in which subjects are predominantly of white european descent. Ben lynch, anaturopathic physician who has focused attention on mthfr polymorphisms and genetic changes, and the linkage to diseases and conditions. 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. Jan, 2016 there are over fifty types of mthfr gene mutations. Nov 30, 2018 the mthfr a1298c polymorphism reduces mthfr enzyme activity to a lesser extent than the mthfr c677t polymorphism.
238 1010 147 36 639 617 1307 1232 988 856 154 621 1246 328 1358 768 1280 926 515 759 925 678 992 409 140 146 1304 915 1064 145 851 284 673 380 370 733 742 495 147