“MTHFR: The Gene That Powers Detox, Mood & More.”

What is Methylation?

Methylation is a natural process in the body where tiny chemical tags called “methyl groups” are added to DNA. These methyl groups are like little on/off switches that can turn genes up or down—basically, they control whether a gene gets activated or silenced.

To make it simpler: Imagine your DNA is like a cookbook with tons of recipes (your genes). Methylation is like putting sticky notes on certain recipes. If you put a sticky note on a recipe, it tells the kitchen (your body) not to use that recipe right now. If there’s no sticky note, the kitchen can make that dish (gene) as usual.

This process is important because it can impact aspects such as your development, health, and even your risk of certain diseases.

The genetic SNPs typically tested for folate metabolism are MTHFR 677T and 1298; however, there are many more. For Alex’s test, only MTHFR C667T and A1298C were tested.

Here are the key SNPs (single-nucleotide polymorphisms) commonly associated with folate metabolism:

🔬 Major SNPs in Folate Pathway

Gene	SNP (rsID)	Effect on Folate Metabolism
MTHFR	rs1801133 (C677T)	Reduces enzyme activity (up to 70% if TT). Leads to higher homocysteine and lower 5-MTHF.
MTHFR	rs1801131 (A1298C)	Also reduces MTHFR activity, but less than C677T. It may still affect methylation if combined with C677T.
MTR	rs1805087 (A2756G)	Affects methionine synthase, which uses 5-MTHF to regenerate methionine.
MTRR	rs1801394 (A66G)	Impacts methionine synthase reductase, required to keep MTR active. Can elevate homocysteine.
SHMT1	rs1979277	Involved in folate cycle—important for converting folate to usable forms.
DHFR	Various, incl. 19-bp deletion	Impacts folic acid conversion; affects folate availability in tissues.
SLC19A1 (RFC1)	rs1051266 (G80A)	Affects transport of folate into cells; may influence folate status.

📌 Most Well-Known: MTHFR C677T & A1298C

C677T (rs1801133): Common in ~10-20% of people (TT genotype) in some populations

A1298C (rs1801131): Often co-occurs with C677T

Compound heterozygotes (one of each variant) may also impair folate metabolism significantly

🧬 Why This Matters:

These SNPs can lead to:

Reduced ability to convert folic acid into active folate (5-MTHF)

Higher homocysteine levels (a heart and brain health risk)

Greater need for activated forms of folate (like folinic acid or 5-MTHF)
Methylation imbalances (affecting mood, detox, gene regulation)

The results can have one of 5 outcomes:

Normal, Mild impact, moderately impacted, severely impacted and beneficial

Overview of the results:

Methylation	MTHFD1	1958 G>A	GA	moderately impacted
	MTHFR	677 C>T	TT	Severely impacted
	MTHFR	1298 A>C	AA	normal
	MTR	2756 A>G	AA	normal
	MTRR	66 A>G	GG	moderately impacted
	CBS	699 C>T	TC	impacted
	COMT	472 G>A	AG	moderately impacted