As i am sure you found out in doing your own research, the a1298c gene variant is found in the mthfr methylenetetrahydrofolatereductase gene. I recently found out that i have compound heterozygous mthfr c677t mutation and a1298c mutation. The health of both male and female at conception will determine how mthfr is impacting your body and to what degree this will then impact the baby. Mthfr polymophisms polymorphism cytosine c is replaced by thymine t at position 677 or adenine a is replaced by cytosine c at position 1298. Heterozygous a1298c seems relatively benign for most people, though heterozygous c677t may be.
As homocysteine promotes brain atrophy, we set out to discover whether people carrying the c677t mthfr polymorphism which increases homocysteine, might also show systematic differences. Other studies showed that homozygous 677tt patients have a. Migraine, with and without aura ma and mo, is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia. I just found out that i have the homozygous a1298c mthfr mutation.
An example of this the most common compound heterozygous situation. The mthfr a1298c polymorphism reduces mthfr enzyme activity to a lesser extent than the mthfr c677t polymorphism. Mthfr c677t and a1298c variant genotypes and the risk of. So, you can see below that the gene variants or the difference between the gene types changes how much the gene mutation a1298c will affect your health, for example. Compound heterozygous mutations occur when you have a copy of both a1298c and c677t. In addition, the compound heterozygosity c677ta1298c was. Mthfr is an enzyme that adds a methyl group to folic acid to make it usable by the body. Mar 11, 2020 mthfr is an enzyme that adds a methyl group to folic acid to make it usable by the body. C677t mthfr gene mutation is the heterozygous mutation due to the presence of one normal c and one abnormal t. The results of genotype frequencies and odds ratios for mthfr genotypes and ms are presented in table 1. Mthfr gene c677t and a1298c variants are associated with. Ben lynch, the leading authority on mthfr in the united states i might have just made that up. The c677t variant in the methylenetetrahydrofolate reductase mthfr gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease.
In vitro studies have shown that the 677tt and 1298cc variant genotypes have 60% and 30% reduced enzyme activity in comparison to the wild type mthfr genotypes. The family history of associated diseases is also common. Mthfr a1298c heterozygous mutation group public group. Estrogenprogestin contraception is not strongly contraindicated in women heterozygous for these mutations, or for assaying for presence of the methylenetetrahydrofolate reductase mthfr 677ct, mthfr 1298 ac. There is also compound heterozygous, which is when you have one mutant allele on both the 677 and 1298 base positions.
Heterozygous mutations one good copy and one bad are mthfr a1298c because there is one normal a and one abnormal c also occasionally written 1298ac. Before i knew this, i was taking methylcobalamin b12 sublingual and no folate. The majority of problems experienced with the a1298c gene mutation are associated with neurotransmitters. Understanding the mthfr mutation basics to health with that. Mthfr c677t and a1298c genotyping was performed by mspcr and pcrrflp methods, respectively. There are two mthfr gene variants, called c677t and a1298c, that have been an active area of study. Prevalence and role of methylenetetrahydrofolate reductase 677 c. Heterozygous and homozygous carriers of the mthfr 677t allele variant have 3040% and 6070% reduced enzyme activity, respectively, as determined by in. Dec 12, 2016 there are two different types of the a1298c gene mutations, these are referred to as heterozygous and homozygous. Mthfr pregancy what you need to know to be successful. Homocysteine is an amino acid linked to a wide range of health problems, and is an independent risk factor for heart. Women of childbearing age should take the standard dose of folate supplementation to reduce the risk of neural tube defects. However, mothers who were heterozygous or homozygous for the mthfr variant and homozygous for the 66ag variant in mtrr 602568.
I am heterozygous for the c677t variant of the mthfr gene, which means i have one copy of the c677t allele. Association of the mthfr a1298c variant with unexplained severe. Of these, mutations on the points at c677t and a1298c seem to have the most clinical significance. There are two options for the gene, a and c, where a c would be a variant. Again, a single copy of a1298c mthfr does not appear to be harmful unless it is combined with the c677t mthfr snp known as compound heterozygous. If you have two copies of the c677t gene this means you are homozygous for this variant then the mthfr enzymes activity can drop by 7075%. Symptoms exist and doctors are saying there is no correlation between the mthfr. May 14, 2016 there is also compound heterozygous, which is when you have one mutant allele on both the 677 and 1298 base positions. Here are your homozygous mutations as indicated in your snp gene table above not including mthfr. Jul 11, 2016 if you have a homozygous c677t variant, the compound heterozygous state or even a single heterozygous single allele mutation, it is very easy to treat with lmethylfolate.
The heterozygous mthfr 1298 gene has a reduced function of approximately 20% and the. Women with this mutation typically show hormonal problems such as menstrual irregularities and mood swings. Second was a 4 12 week natural miscarriage or chemical pregnancy. Ben lynch, the leading authority on mthfr in the united states i might have just made that up but hes seriously ace. Mthfr polymorphism testing is frequently ordered by physicians as part of the clinical evaluation for thrombophilia. A common genetic variant that may speaking of women. You mentioned that you are heterozygous for a1298c. Sign in here to access free tools such as favourites and alerts, or to.
Simply being heterozygous means that you have one mutated copy of an allele which holds a particular variant and one normal allele. I have mthfr c677t mutation what to health with that. There are two different types of the a1298c gene mutations, these are referred to as heterozygous and homozygous. Further, mthfr is the short gene name that code for enzyme which alters the folic.
Mar 21, 2018 heterozygous mthfr a1298c is thought to have mostly normal mthfr activity and homozygous mthfr a1298c c1298c have about 65% normal activity so 35% compromise. These are generally not as bad as red homozygous mutation, but they may still worth paying attention to. Back to list of questions question question listen. Association between mthfr genetic variants and multiple. Illustrative examples of genotype analysis of the two mthfr variant genotypes are shown in fig. In this study, individuals who were homozygous for the c677t. Cardiovascular disease, stroke, heart attack, and deep vein thrombosis. If you have a homozygous c677t variant, the compound heterozygous state or even a single heterozygous single allele mutation, it is very easy to treat with lmethylfolate. The routine lab test for mthfr variant only reports on 677 and 1298 as these are the most studied. Mutations can affect one heterozygous or both homozygous of these genes. Normal activity refers to the way your body converts folic acid to 5lmethyltetrahydrafolate the active form so that it can be used. Anyone have the mthfr homozygous a1298c gene mutation.
Important mthfr pregnancy points the dna health and nutrition stores are passed onto the fetus upon conception, along with the mthfr gene mutation. This enzyme is also important for converting homocysteine into methionine, which the body needs for proper metabolism and muscle growth and which is needed for glutathione. Unlike mthfr c677t, mthfr 1298 is not linked to elevated homocysteine levels unless there is a heterozygous mthfr 1298 and mthfr 677 together. After our last loss, my dh dear husband and i took a long gap to prepare ourselves for another chance at pregnancy. Estrogenprogestin contraception is not strongly contraindicated in women heterozygous for these mutations, or for assaying for presence of the methylenetetrahydrofolate reductase.
In america, about 25% of people who are hispanic, and 1015% of people who are caucasian have two copies of c677t. Mthfr tells our body how to create an enzyme involved in breaking down the amino acid homocysteine. There are two common types, or variants, of mthfr mutation. In this piece, ill address some of the questions ive received since then, including the variant i have, how it affects migraine presentation, and what steps others can take to learn more. Mthfr is actually a very common genetic defect that affects nearly 50% of people mildly and approximately 25% of people seriously. In addition, despite increased risks of some conditions, having a specific mthfr mutation has been associated with a lower risk of acute lymphatic leukemia all and some.
The normal wild type cc mthfr gene gives instruction for production of the methylenetetrahydrofolate reductase enzyme. Men also have hormonal problems such as bad acne and the inability to sit still. Mthfr gene variant genetic and rare diseases information. Thankfully, single heterozygous mutations, may minimally affect feelings of overall health.
Remember, if you are homozygous a1298c or compound heterozygous mthfr, the likelihood of your family members also having mthfr mutations is very high. One of the biggest concerns for those with an mthfr mutation is the effect it may have on homocysteine levels in the blood. Two common polymorphisms are reported, c677t and a1298c, that are implicated in a number of human. After many years of no cause found, i now have been diagnosed with mthfr gene mutation privately. However, the homozygous cc a1298c polymorphism of the mthfr gene was present at a statistically high significance in severe. This is no longer theory as current research supports it. This genotype is associated with intermediate levels of enzyme activity, but is not causative for an increase in plasma. The mthfr gene is important in the metabolism of homocysteine, an important amino acid. Jun 11, 2017 mthfr a1298c heterozygous 2030% loss of function.
Disruptions in both mthfr genes may lead to lower levels of tetrahydrobiopterin bh4. Homozygous 2 copies of the gene, one each from your father or mother. Normal activity refers to the way your body activates your folic acid so that it can be used, so compromise usually looks like a functional folate deficiency. Mthfr a1298c heterozygous mutation group has 1,211 members. Common folate gene variant, mthfr c677t, is associated with. Combined genotype and haplotype distributions of mthfr c677t. If you already know what mthfr is, perhaps you know that you have a variant of this gene such as c677t or a1298c.
Further, mthfr is the short gene name that code for enzyme which alters the folic acid to active state, which is used by the body. Methylenetetrahydrofolate reductase mthfr c677t and a1298c. Sep 25, 2011 this theory is born out of wondering why some women are experiencing recurrent pregnancy loss, have had all sorts of laboratory and physical tests done yet the only thing that shows up is a heterozygous a1298c mthfr mutation or a heterozygous c677t mutation along with a normal homocysteine level. The 677 variant is associated with early heart disease and stroke and the 1298 variant with a variety chronic illnesses. Its also possible to acquire both c677t and a1298c mutations, which is one copy. Addressing genetic counseling dilemmas using evidence. In people who are heterozygous for an mthfr c677t mutation, there is. Mthfr c677t mutations hypertension in homozygous c677t mthfr individuals. Nov 30, 2011 remember, if you are homozygous a1298c or compound heterozygous mthfr, the likelihood of your family members also having mthfr mutations is very high. Currently, over 40 point mutations of this gene have been identified. Homozygous a1298c two bad copies can also be written as c1298c because there are two abnormal copies with c instead of a. Mthfr c677t mutation is a genetic variation and a single nucleotide polymorphism snp found in the mthfr gene.
Welcome to the mthrf a1298c heterozygous mutation group. There are over fifty types of mthfr gene mutations. Methylenetetrahydrofolate reductase mthfr is a key enzyme in the folate metabolic pathway. The mthfr gene produces this enzyme that is necessary for properly using vitamin b9. I had a test done earlier this year and my b12 was high at 1164 range 145670 and folate was 10 range 5. Common folate gene variant, mthfr c677t, is associated. I regret the long gap as i have turned 40 and we dont have any children. The first was a possible, but never confirmed, ectopic. It is against the law to copy and paste as if its your way of presenting this information. For those who have the a1298c mthfr mutation, this is frustrating.
However, the two that are most commonly studied and tested for are c677t and a1298c. It has been suggested that mutations in mthfr, which alter both dna methylation and nucleotide synthesis, are related to crc incidence 7, 8. Jan, 2016 there are over fifty types of mthfr gene mutations. A commonly carried c677t polymorphism in a folaterelated gene, mthfr, is associated with higher plasma homocysteine, a wellknown mediator of neuronal damage and brain atrophy. Methylenetetrahydrofolate reductase mthfr is involved in amino acid synthesis and dna function. How the mthfr gene mutation affects my physical and mental. Jul 19, 2016 heterozygous mthfr c677t have about 65% normal mthfr activity so 35% compromise and homozygous mthfr c677t t677t have about 30% normal activity so 70% compromise. Heterozygous 1 copy of the gene from your father or mother. If you have one copy of this gene heterozygote then activity can be reduced by 3335%.
There is little known about the a1298c mthfr mutation. Two polymorphic variants, c677t and a1298c, in the mthfr gene were first. I had a test done earlier this year and my b12 was. Being homozygous for mthfr a1298c leads to 60% of normal. We aimed to test the hypothesis that c677t and a1298c variants of mthfr predispose to microsatellite instable msi colorectal cancer. The test results could comeback as an individual having two copies of the a1298c mutations homozygous or have one copy heterozygous or non at all.
Heterozygous mthfr a1298c is thought to have mostly normal mthfr activity and homozygous mthfr a1298c c1298c have about 65% normal activity so 35% compromise. To determine the prevalence of mthfr variants and their potential relevance. While there are many fb groups out there for those learning that they have mthfr and other gene variants, this forum is. We determined mthfr genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in shiraz, southern iran. I just found out i have a mthfr homozygous a1298c mutation the c677t mutation was not detected. The problems experienced by the c677t gene mutation are more likely to have elevated homocysteine. Both the c677t and a1298c variant genotypes of mthfr have been associated with decreased enzyme activity, with the c677t having a more severe effect than the a1298c variant.
Interaction of mthfr c677t and a1298c, and mtr a2756g gene. A1298c the other mthfr mutation we test for is for the a1298c. In 2003, a genetic study called the human genome project was completed. I personally have one little heterozygous mthfr 1298 mutation but guess what. First read my theory below and then i will provide the proof.
A pediatrician goes indepth into mthfr checkup newsroom. The enzymatic activity of mthfr in people with one minor allele in each mthfr c677t and a1298c polymorphisms is lower than the activity. The genotype groups tt, ct, and cc did not differ in any demographic or clinical characteristics, for the adni and chs cohorts, respectively. The methylenetetrahydrofolate reductase gene variant c677t. What does this mean for treatment and further testing recommendations. What is the clinical significance of the mthfr a1298c. Reduction in systolic and diastolic blood pressure using riboflavin downs syndrome etiology linked to mothers with. There is also a c677t which seems to get more attention, but i found that symptoms associated with mthfr mutations include. When we identify a part of the sequence that varies, we call it a variant.
Mthfr c677t homozygous 6070% loss of mthfr function. I cannot believe i just wrote all that out, given my limited genetic knowledge. Homozygous means you have two identical mutated copies of the same gene with the variant. It was previously hypothesized that reduced enzyme activity of mthfr led to. Sep 27, 2017 current clinical guidelines do not recommend changes in prenatal care or prenatal vitamins based upon mthfr gene variant status alone. Two common variant genotypes of the mthfr gene, c677t in exon 4 ala222val and a1298c in exone 7 glu429ala, are associated with reduced enzyme activity 5,6. Its the associated single nucleotide polymorphisms attached.
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