It is my favorite time of the year in Alaska. Summer means sunshine and warmer weather. Summer means agate hunting on the beach and seagulls squawking as they fly overhead. Summer means LIFE. I just love summer~
This summer has been filling up with busy days enjoying the weather as well as good company. I tend to go-go-go and it is a good feeling by comparison of my near hibernation in winter. It’s nice to have more energy to do things and live a little; even if it’s just somebody else’s ‘normal’.
Millennium Pharmacogenetic Testing (PGT)SM can help health care professionals more effectively personalize treatment by identifying patients who may benefit from a modified drug selection or dose of certain prescribed medications.
The test was primarily to test my genetic compatibility with different medications; such as Amitriptyline (Elavil) which I already take a daily dose of before bedtime to try to prevent migraines on a daily basis. The test showed that I metabolize it normally. It screened me for others with a note as to the genetic impact each would have on me. One that did pop up stating that I would benefit from taking it is for L-Methylfolate (Deplin). This is genetically important for the MTHFR gene. What is the MTHFR gene, one might ask? I know I certainly had to google it later!
Methylene tetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer’s disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylene tetrahydrofolate reductase deficiency.
Yeah, so turns out I have a mutated form of the MTHFR gene which can lead to a whole bonanza of health issues. It could be why I have such terrible migraines, C.V.S., childhood cancer, and so much more in the family medical history. That is HUGE news! It has to be pertinent information to more than just myself as it is genetically inherited too. So this could be something that affects my sisters, my mom, my daughter… and maybe more family depending on if it was inherited from one or both of my parents.
I took a 23andMe dna test last October and it provides RAW data on my DNA results, I decided to look into what it has to say about my MTHFR genes. If you already have a 23andMe account just log in and hop over to their tools section and select the ‘browse RAW data’ selection in the drop down menu bar.
Search for specific genes and markers (SNPs) of interest.* You can view or download your data at anytime in its raw, uninterpreted format (your A’s, T’s, G’s, and C’s).
Using the raw data I could seek the MTHFR gene solely from the DNA collected. Mind-boggling would be an understatement! Once that was in front of me on the screen I saw it all…. and honestly wished I had kept my Biology 1 and 2 notes from high school! Genes, markers (SNP), genomic position, variants and genotypes galore. What did all that mean?!
Thankfully I had been busy communicating in a message feed with my sisters and mom. My younger sister was on it! She sent me links to a few excellent blogs AND a site called genetic genie which uses your 23andMe raw data to explain your very own methylation analysis results! Praise the Lord! This site was able to break it down in simpler terms for me and it makes way more sense than it did a few days ago. The genetic genie states that I have one homozygous (+/+) mutation and five heterozygous (+/-) mutations along with several normal MTHFR genes out of the SNP markers found in my raw data. The homozygous mutations from my SNP gene table (not including the normal MTHFR) are CBS A360A and my heterozygous mutations from my SNP gene table (also not including the MTHFR) are COMT V158M, COMT H62H, VDR Bsm, VDR Taq, and MTRR A66G.
The homozygous (+/+) mutation means that both copies I have inherited from my parents (mother and father) are mutated. The heterozygous (+/-) mutation means that only one gene inherited from my parents is mutated. Then the SNP showing (-/-) is normal inherited genes or un-mutated.
The heterozygous mutation (MTHFR C677T ; C/T; +/-) which they state via my SNP gene table are COMT V158M, COMT H62H, VDR Bsm, VDR Taq, and MTRR A66G. I haven’t quite figured out what all those mean yet, but there is information on MTHFR C677T at least being that it is the more common mutation. It is to help convert homocysteine to methionine except the mutation causes the MTHFR enzyme to have trouble activating the folate being consuming. This can lead to high levels of homocysteine and cause many health problems not limited to but including chronic fatigue syndrome, Bipolar Disorder, Autism, Fibromyalgia, MS and much more chronic health conditions. They state that as S-adenosylhomocystein (SAH) accumulates, the COMT enzyme might become impaired. This can increase dopamine levels in COMT V158M (-/-), but for those with COMT V158M (+/+), the high level of SAH can lead to behavioral problems and mood swings (according to the quote on my genetic genie info which is quoting a Dr. Amy Yasko).
Genetic Genie also states:
MTRR (Methionine synthase reductase) helps recycle B12. The combination of MTR and MTRR mutations can deplete methyl B12. MTR A2756G, MTRR A66G, MTRR H595Y, MTRR K350A, MTRR R415T, MTRR S257T, and MTRR A664A all work together to convert homocysteine to methionine.
MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) provides instructions for making the enzyme methionine synthase. Methionine synthase helps convert the amino acid homocysteine to methionine. To work properly, methionine synthase requires B12 (specifically in the form of methylcobalamin). An MTR A2756G mutation increases the activity of the MTR gene causing a greater need for B12 since the enzyme causes B12 to deplete since it is using it up at a faster rate. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency. Megaloblastic anemia can occur as a consequence of reduce methionine synthase activity.
A homozygous mutation of MTR A2756G is not very common (<1% of CEU population). Some studies have demonstrated that people with a combination of MTHFR C677T and MTR A2756G have persistently high homocysteine levels unless they are treated with both B12 and folate.
COMT (catechol-O-methyltransferase) helps break down certain neurotransmitters and catecholamines. These include dopamine, epinephrine, and norepinephrine. Catechol-O-methyltransferase is important to the areas of the pre-frontal cortex. This area of the brain is involved with personality, inhibition of behaviors, short-term memory, planning, abstract thinking, and emotion. COMT is also involved with metabolizing estrogens.
COMT (-/-) individuals can usually break down these neurotransmitters efficiently, but COMT (+/+) individuals may have trouble breaking these chemicals down from impaired function of the enzyme. With a COMT + status, it has been clinically observed by physicians that people may have trouble with methyl donors. This can lead to irritability, hyperactivity, or abnormal behavior. They may also be more sensitive to pain.
VDR (Vitamin D Receptor) encodes the nuclear hormone receptor for vitamin D3. Low or low normal vitamin D values are often seen in those with chronic illness and even the general population. Low vitamin D is related to a lot of neurological and immunological conditions. Vitamin D stimulates enzymes that create dopamine.
VDR Tak and VDR Bsm are usually inverse from eachother. So if there is a (+/+) VDR Tak, there would be a (-/-) VDR Bsm. However, this is not always the case.
It has been clinically observed that the body may have trouble tolerating methyl donors with a COMT V158M + and a VDR Taq + status. VDR Taq (-/-) individuals may already have higher levels of dopamine, and combinations of variations COMT and VDR Taq can lead to a wide range of dopamine levels. Those that are VDR Taq (+/+) and COMT (-/-) may have lowest dopamine levels.
Note: Some have pointed out that VDR Taq is reported backwards since majority of medical journals report a different risk allele or use different notation. These arguments are well-founded, but Genetic Genie reports this way so results are compatible with existing methylation nutrigenomics literature. Many claims about VDR and methylation are clinical observations. There are no medical studies to support some of the observations.
As for my homozygous mutation (CBS A360A; A/A; +/+) according to genetic genie states:
CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine. CBS defects are actually an upregulation of the CBS enzyme. This means the enzyme works too fast. In these patients, it’s common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine. This leads to high levels of taurine and ammonia. The CBS upregulation has been clinically observed to result in sulfur intolerance in some patients. It has also been observed that BH4 can also become depleted with a CBS upregulation. BH4 helps regulate neurotransmitters and mood. Other mutations, such as MTHFR A1298C, Chronic bacterial infections, and aluminum can also lead to low BH4 levels. Lack of BH4 can lead to mast cell degranulation and possibly mast cell activation disorder (MCAD).
Note: While some physicians think the CBS mutation is one of the most important mutations to address, there is very little medical research to support these claims and some doctors in the field disagree. In normal populations, studies have shown CBS upregulations to be protective against high homocysteine. However, CBS upregulations have shown to be harmful in Down Syndrome. Medical research has not determined if CBS upregulations are harmful in those with syndromes or disorders leading to impaired methylation.
Thanks to Genetic Genie, I am far more eager to start working on Deplin and seeing where that takes me. I plan to discuss it further with my primary doctor and possibly the neurologist (if I can get my butt to Anchorage anyhow… SO not a city driver… but it could be arranged thanks to others who do city driving haha). I would need to be on Deplin probably long term as this is dealing with the genetic mutation and filling gaps that it is creating in my health as far as folate is concerned (which is a lot). I plan to look into more B vitamins and whatever else would need to be optimized considering the health gaps thanks to mutated genetics 🙂
But honestly, reading about what all can and often does go wrong when one has these mutations…. made me SO thankful to God. When I was pregnant with Riley… I prayed. I prayed a lot for a healthy baby and I know that is something all parents generally do; but I was constantly worried about my cancer history. All I could think about was doctors telling me that it could have been a genetic cancer and that if I ever became pregnant and successfully gave birth to a child that that DNA would be passed on… possibly resulting in my child(children) also developing cancer. That is a lot to consider. That is a lot of guilt to carry into pregnancy and parenthood. I kept praying, “Lord, please protect and heal this baby. Please don’t let it inherit my damaged dna. Please don’t let this child go through chemo and cancer like I had to…. and my family had to…. please protect my baby!” I was desperate to know the peace that only God can impart when there is that much on the line. I didn’t care boy or girl. I didn’t care about eye color, hair color, or anything as long as the baby could be healthy. I didn’t even know I had cancer until I was 8 years old. I lived fairly healthy a life without any obvious signs of cancer or illness until probably age 6 or 7. When you are a parent and trying to do your best it is hard to not worry. It was not obvious signs. Not before… and now I do know that my mom has gone back through old photos and notes of our lives back before cancer… and she sees things… the signs of illness creeping into my face and my life. I know that hurts her. How could it not? I know that she did her best, and I am SO grateful to her for being the mom she was and is to me. I cannot imagine going through that with my own child. I truly hope that Riley, my daughter, progresses truly normal and healthy as the years go on. She is seven now… and honestly… I still pray that God has spared her those bad genes. As I read about the MTHFR stuff… I know God has spared our family generation after generation of horrible affects. It hasn’t been all roses, but it has been far better than it could have been. I mean it. MTHFR is SO important in our bodies. FEARFULLY and WONDERFULLY MADE~ it’s true.
So despite the illness, despite the raindrops falling on you today; look around! Be grateful to God and bring Him glory in all that you are and all that you do. If you aren’t sure how to get above and beyond the hardships… PRAY. Wait upon the Lord and He will answer you. He ALWAYS answers. Sometimes it comes quickly and sometimes it trickles in. That is ok. Just never ever forget how much God loves you and wants the best for you. Read your bible, fellowship with others, sing praises with others and on your own…. God is GOOD <3
God is so good.