It’s good to work with a health care practitioner who really understands genes, they’re complicated! Buckle up, let’s look at a few details.

I’d like to talk about two different gene topics, BOTH demonstrating the importance of the golden rule: genes never work alone, it always matters

1. What other genes you have and
2. Your lifestyle choices that weaken or strengthen the effects of the gene

Language:
All genes have an influence on your life by modifying real life events. Those old familiar X and Y genes determine your sex at birth. All X’s and Y’s are pretty much the same. It’s how they pair up, the one from mom and the one from dad.

VARIANTS:
The one we frequently talk about in this newsletter is the ApoE4 gene. Again, the ApoE genes (E2, E3 and E4) are the same within each group, but since they come in three forms, they are all considered “variants” of ApoE. We’ll get back to that one.

Most pairs of genes, though, are both named the same, but those two same-named genes come in two different forms. One is considered the wild type and one is the variant.

For shorthand, we label them -/+ (wild/variant).

Having one or two variants in a given gene can influence your body’s interaction with the world.

METHYLATION GENES:
Let’s start with the MTHFR genes. Two different ones, they go by the numbers A1298C and C677T, and they have different implications.

A1298C variants suggest that your body needs special forms of vitamins B12 and B9, forms that have methyl (carbon with 3 hydrogen atoms: CH3) attached to them.

MOST vitamins have B12 in the form cyanocobalamin (cyano-B12) and B9 as folic acid.

Serious concern about A1298C variants suggests one might benefit from methylcobalamin (methyl-B12) and methylfolate (methyl B9).

C677T variants suggest all the same cautions about methyl need, with additional quirks, two important ones:

You might also need extra vitamin B2 (riboflavin) to help your B’s do all their jobs

When it comes to folate, you might benefit from both methylfolate and folinic acid. You’ll never see that on the label of a drug store vitamin

Can we do one more variant?

The COMT variants, especially with two variants (+/+, also called Met/Met), are slow to handle your otherwise very valuable methylated B vitamins.

OK, slow isn’t always bad, but in this case what gets slowed down is your body recycling your neurotransmitters.

As they build up waiting to be recycled, they can cause anxiety, irritability, mood swings, and insomnia.

• Insomnia! We’re always looking for more ways to improve sleep. Maybe if you have COMT variants, it would be good to cut back a little bit on methylated B’s
• As if that weren’t enough, there’s another reason: Brilliant nutritional expert Chris Masterjohn, PhD, points out that if you have too many methyl groups, THEY are piling up to be recycled as well.

The enzyme that does that (GNMT) uses up a valuable amino acid glycine.

What is glycine used for?

Oh, just for healthy collagen, skin, and sleep!

Masterjohn goes on to recommend some of my faves: food sources of choline and folate (eggs and liver) and supplementing with both glycine (I choose PM) and creatine (daytime)

He has his own column, but you can check him out on this podcast if you’re interested.

APO E GENETICS
Let’s go on to the ApoE4 gene. Even though it is way more complicated than MTHFR, the ApoE4 gene interacts with over 1700 other genes, I just want to talk about one simple interaction, and it’s not even genetic.

First, let’s go over the basics:

• The ApoE2 gene might raise your cholesterol, but it does NOT seem to raise cardiovascular risk and it lowers your risk of Alzheimer’s type dementia
• The ApoE3 gene is the wild type so you have standard risks of cardiovascular disease or Alzheimer’s
• The ApoE4 gene gives you high cholesterol, more cardiovascular risk and a significantly increased risk of Alzheimer’s

I want to take that last comment back to the X and Y sex comments above.

• High cholesterol affects both sexes equally
• Cardiovascular risk is boosted more for men up to a certain point. Past menopause, women catch up with men and perhaps surpass them in cardiovascular risk
• Alzheimer’s risk is dependent on whether you have 1 or two copies of the E4
  • Men’s risk is barely increased with one variant, but about TEN TIMES with two variants
  • Women’s risk is boosted 3 to 4 times with one variant and 10 to 15 times with two variants, especially after menopause, especially after menopause with inadequate attention to hormones, not just estrogen but all the hormones that interact with estrogen as well

Whew, if you’ve stayed with the conversation this long, hats off to you. It’s complicated.

If you’re intrigued and want to learn more, please consider an appointment with Dr. Mehrens, or myself if you’re an established patient.

And of course, tune into the Alzheimer’s prevention conference where I talk completely about hormones and dementia risk management, not ignoring men’s needs but with greater emphasis on women in menopause.