📊 Executive Summary
Methylation Genes
9 Tested
Endocrine Genes
21 Tested
Methylation Variants
2 Found
MTRR AG • COMT CC
Endocrine Variants
10 Found
All heterozygous
🧪 Methylation Pathway Analysis
Methylation is a fundamental biochemical process that regulates gene expression, detoxification, neurotransmitter synthesis, and cardiovascular health. Proper methylation depends on a coordinated network of enzymes and transporters, primarily fueled by the folate-methionine cycle. Variants in key methylation genes can influence enzyme efficiency and the body's ability to maintain healthy homocysteine levels, produce neurotransmitters, and support cellular repair.
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs1801133 | MTHFR | C677T | GG | Normal | Homozygous common — normal MTHFR enzyme function |
| rs1801131 | MTHFR | A1298C | TT | Normal | Homozygous common — normal MTHFR enzyme function |
| rs1805087 | MTR | A2756G | AA | Normal | Homozygous common — normal methionine synthase |
| rs1801394 | MTRR | A66G | AG | ⚠️ Heterozygous | One G risk allele — moderately reduced MTRR activity |
| rs4633 | COMT | Val108/158Met | CC | ℹ️ Met/Met | Low COMT activity — higher dopamine, more SAMe available for methylation |
| rs6269 | COMT | Intronic | GG | Normal | Homozygous common |
| rs3733828 | BHMT | — | GG | Normal | Homozygous common — normal betaine pathway |
| rs2236225 | MTHFD1 | — | GG | Normal | Homozygous common — normal folate one-carbon metabolism |
| rs4402960 | RFC1 | — | GG | Normal | Homozygous common — normal folate transport |
Methylation Status: Generally Favorable
The most critical methylation gene, MTHFR, shows no risk variants at either major positions (677T and 1298C), indicating normal folate-methionine cycle function. The MTRR A66G heterozygous variant may moderately reduce enzyme recycling of methionine synthase, but this is often manageable with B12 and folate intake. The COMT Met/Met (CC) genotype is notable — it means lower COMT enzyme activity, leading to higher dopamine levels and more SAMe (the primary methyl donor) available for methylation reactions. While this is technically a "variant," it is not necessarily adverse and may even be beneficial for methylation capacity.
⚖️ Endocrine Pathway Analysis
The endocrine system governs hormone production, metabolism, stress response, thyroid function, and reproductive health. Genetic variants in endocrine-related genes can influence hormone sensitivity, receptor function, metabolic efficiency, and the body's response to environmental stressors. The following analysis covers six key endocrine categories.
🦋 Thyroid
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs225014 | DIO2 | Thr92Ala | CT | ⚠️ Heterozygous | Reduced T4→T3 conversion efficiency |
| rs2275593 | TPO | — | TT | Normal | Homozygous common — normal thyroid peroxidase |
🧠 Stress / HPA Axis
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs3800373 | FKBP5 | — | AC | ⚠️ Heterozygous | Altered glucocorticoid sensitivity |
| rs1360780 | FKBP5 | — | CT | ⚠️ Heterozygous | Altered HPA axis regulation |
💊 Sex Hormones
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs9340799 | ESR1 | — | AG | ⚠️ Heterozygous | Altered estrogen receptor alpha |
| rs2283228 | SHBG | — | AC | ⚠️ Heterozygous | Potentially lower SHBG, higher free sex hormones |
| rs1042713 | GPER1 | — | AG | ⚠️ Heterozygous | Altered rapid estrogen signaling |
| rs61762127 | ESR1 (eSNP) | — | CC | Normal | Homozygous common |
| rs7496 | CYP19A1 | — | CC | Normal | Homozygous common — normal aromatase |
| rs10046 | CYP19A1 | — | AA | Normal | Homozygous common — normal aromatase |
🍽️ Metabolic
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs2275593 | TCF7L2 | — | CT | ⚠️ Heterozygous | Increased insulin resistance risk |
| rs2241766 | ADIPOQ | — | GT | ⚠️ Heterozygous | Altered adiponectin levels |
| rs1501299 | ADIPOQ | — | GG | Normal | Homozygous common |
☀️ Vitamin D
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs2282679 | GC (VitD BP) | — | GT | ⚠️ Heterozygous | Altered vitamin D binding affinity |
| rs731236 | VDR | FokI | AA | Normal | Homozygous common |
| rs1544410 | VDR | TaqI | CC | Normal | Homozygous common |
| rs2228570 | VDR | BsmI | GG | Normal | Homozygous common |
🌙 Circadian
| SNP | Gene | Variant | Genotype | Status | Significance |
|---|---|---|---|---|---|
| rs10830963 | MTNR1B | — | CC | Normal | Homozygous common — normal melatonin receptor |
Endocrine Status: Several Mild Variants Detected
All 10 endocrine variants are heterozygous — meaning only one copy of the variant allele is present. This typically results in a mild or moderate effect rather than a severe impairment. The two FKBP5 variants together suggest potentially altered stress hormone (cortisol) sensitivity, making stress management and sleep hygiene particularly relevant. The DIO2 Thr92Ala heterozygous variant may slightly reduce thyroid hormone conversion. The GC variant suggests attention to vitamin D status through regular blood testing. Overall, these variants point toward lifestyle optimization rather than medical intervention.
🚫 Untestable Genes (Not on 23andMe Chip)
23andMe's genotyping array covers ~600,000 SNPs but does not include every medically relevant gene. The following key genes — important for methylation and endocrine health — are not tested on the 23andMe platform.
Methylation Pathway Genes Not Tested
- DHFR Dihydrofolate reductase — key folate metabolism
- SHMT1 Serine hydroxymethyltransferase — one-carbon metabolism
- CBS Cystathionine beta-synthase — transsulfuration pathway
- GNMT Glycine N-methyltransferase — SAMe regulation
- TCN2 Transcobalamin II — vitamin B12 transport
- BHMT2 Betaine-homocysteine methyltransferase — betaine pathway
Endocrine Pathway Genes Not Tested
- TSHR TSH receptor — thyroid-stimulating hormone
- DIO1 Type 1 deiodinase — peripheral T4→T3 conversion
- INS Insulin gene — glucose metabolism
- IGF1 Insulin-like growth factor 1 — growth & metabolism
- NR3C1 Glucocorticoid receptor — stress hormone response
- ESR2 Estrogen receptor beta — hormone regulation
- CYP17A1 Steroid synthesis enzyme — sex hormone production
- LEPR Leptin receptor — appetite & energy regulation
💡
These genes would require specialized testing such as whole genome sequencing (WGS) or a custom targeted gene panel for analysis. If any of these genes are of particular interest, consult with a genetic counselor or functional medicine practitioner about expanded testing options.
💡 Key Takeaways & Actionable Insights
1
Optimal MTHFR status is a major advantage. You carry no risk variants at the two most important MTHFR positions (C677T and A1298C), meaning your core folate-methylation cycle operates efficiently. This is a strong genetic foundation for cardiovascular health and neurotransmitter balance.
2
MTRR A66G heterozygous variant may moderately reduce methionine synthase recycling. Consider ensuring adequate vitamin B12 (methylcobalamin) and selenium intake, which support MTRR function.
3
COMT Met/Met (CC) genotype means lower dopamine breakdown. This is associated with higher baseline dopamine and more SAMe available for methylation. Be mindful of stimulant sensitivity and consider tyrosine-rich foods and stress-reduction practices.
4
Dual FKBP5 variants suggest heightened cortisol sensitivity and altered stress resilience. Prioritize stress management (meditation, exercise, sleep hygiene) as your HPA axis may be more reactive to psychological and physiological stressors.
5
DIO2 Thr92Ala heterozygous may reduce T4-to-T3 thyroid hormone conversion. If you have thyroid symptoms, request a full thyroid panel (TSH, free T3, free T4, reverse T3) from your physician.
6
GC (vitamin D binding protein) heterozygous variant suggests potentially altered vitamin D transport and utilization. Regular 25-OH vitamin D blood testing and supplementation as needed is recommended to maintain optimal levels (40–60 ng/mL).
7
Several untestable genes (DHFR, SHMT1, CBS, etc.) could reveal additional methylation and endocrine insights. If you want a more comprehensive picture, consider whole genome sequencing or a specialized nutrigenomics panel for follow-up testing.