MTHFR mutations are just starting to be recognized as an issue and so more and more doctors are testing, but what happens if your doctor tells you that you’re homozygous for MTHFR A1298C? They might as well be speaking Greek! So here’s the skinny on what that really means. Also here’s a post about MTHFR mutation basic in general.
MTHFR A1298C Terminology Basics (or as basic as we’re going to get with genetics).
The simplest level of information here is just the plain genetics. Here are some quick factoids to get us started:
- MTHFR is the short name for the genes that code for the enzyme that changes folic acid to the active form that your body uses (the long name is methylfolate reductace).
- 1298 is the marker for one particular MTHFR gene.
- The official genetics labeling of this gene is Rs1801131. Sigh.
- You get one copy of this gene from your mother and one from your father, so there are two possible copies that can be either “normal” or “mutant”
- If you inherited one good copy and one bad copy that’s called “heterozygous A1298C”
- If you inherited two bad copies (one from each parent) that’s called “homozygous A1298C”
- A…C stand for the bases that you actually have. A = adenine C = cytosine. Bases are essentially the letters that spell out your genetic code. There are four of them commonly (C, T, A and G).
- When this gene is “normal”or “wild type” (I love that name) it looks like MTHFR A1298A.
- 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.
- Homozygous A1298C (two bad copies) can also be written as C1298C (because there are two abnormal copies with C instead of A). Occasionally you’ll also see it written 1298CC
Phew! So the take-away there is MTHFR A1298C means you have at least one bad copy of this gene, and if it’s called homozygous, or C1298C then you have two bad copies.
How Much of a Problem Is This?
The MTHFR A1298C mutation is considered less serious than the C677T mutation because it seems to cause less impairment to actual methylation function than C677T. That doesn’t in any way mean that it isn’t an issue. This mutation can still be a significant problem If you don’t have a good diet, don’t take supplements or burden your body with a lot of stressors like smoking, alcohol, drugs, sedentary lifestyle or high stress. If you get lots of dark green leafy veggies, legumes and other food sources of natural folate – see this post – then you’re probably already getting good methylfolate. If your diet isn’t up to scratch, then supplementation can be useful and here’s a whole post about that.
Heterozygous MTHFR A1298C is thought to have mostly normal MTHFR activity and homozygous MTHFR A1298C (C1298C) have about 65% normal activity (so 35% compromise). Normal activity refers to the way your body converts folic acid to 5-L-methyltetrahydrafolate (the active form) so that it can be used. Compromise in this case looks like a folate deficiency.
What Are The Health Risks of MTHFR A1298C Mutation?
According to SNPedia, which compiles research on genetics, A1298C mutants have been shown in at least one research study to have an increased risk for:
- Midline defects such as:
- Cleft lip
- Cleft palate
- Neural tube defects
- Facial asymmetries
- Cancers including:
- Head and neck
- Cardiac-related issues including:
- Thrombosis (increased tendency to clot inappropriately)
- High homocysteine levels (a heart risk)
- Pre-eclampsia (dangerous high blood pressure in pregnancy)
- Vascular dementia
- Fertility issues including:
- Multiple pregnancy loss
- Low sperm count
- Birth defects such as down syndrome
- Neurological issues including:
- Alzheimer’s dementia
- Mood and psychological issues including:
You’ll notice that this is quite a list, and it can be a little daunting to think about when you’re just learning about this. Most research doesn’t differentiate between the A1298C genetic variance and the C677T genetic variance so the list is the same for both mutations. We assume the risk is lower with A1298C because the folate metabolism is less strongly impaired, but that might not be correct.
What Do You Do About This?
Compromise with the MTHFR A1298C gene can have severe consequences so it’s important to work on getting good sources of natural folate from foods, which is generally useable by mutants, or 5-MTHF (5-methyltetrahydrofolate) which is already methylated so the genetic compromise doesn’t matter. As discussed in this article, I feel supplementation should be started slowly because for many mutants who haven’t had active folate very much in their lives it feels really strange when those active forms start showing up. There can be quite an adjustment reaction by your body.
Activated folate is used by your body to run enzyme pathways, to aid in some parts of normal metabolism, to help your body detoxify and even to methylate your DNA. The methylation cycle is also a big part of neurotransmitter manufacture, which explains the strong link to depression, anxiety, and mental disorders including addictions and even schizophrenia. If 5-Methylfolate isn’t there then your body does maintains those functions as best it can, but the things your body can’t do start to pile up. Starting supplementation means your body can start digging in that pile to clear up high priority items. This is exactly what we want, but if you start with high doses of a supplement then it’s a little like drinking from the firehose. Kind of out of control and not very pleasant.
A great way to start if you’re unsure, is with a folate-rich diet. I love this image because it kind of covers what we’re looking for. Hint – think dark greens and beans. 🙂
Can Mutants Become “Normal”?
If you’re a mutant (like me) then you’ll always be a mutant, but it doesn’t have to matter. Essentially as long as you’re getting enough of the active form of folate and taking care of yourself for the other consequences of the MTHFR mutation then the mutation doesn’t have to matter. If you aren’t taking care of yourself, then it matters a lot.
The bottom line is MTHFR A1298C mutations don’t have to mean anything at all as long as you supplement and have a good diet and lifestyle (here’s an article about a folate-rich diet for MTHFR mutants) I always suggest taking a little more care with yourself too. There are known health risks for things like clotting, fertility and cancers so it makes sense to take some precautions. Eat your fiber, do your exercises, get your sleep and generally treat yourself with high regard – shouldn’t we all anyway?