VDR Gene and Neurotransmitter Balance: What Your rs731236 Genotype Means

The VDR gene encodes the vitamin D receptor, a protein that helps cells respond to vitamin D. VDR signaling influences many processes, including immune regulation and the production of neurotransmitters such as dopamine and serotonin. These neurotransmitters require tetrahydrobiopterin, or BH4, as a cofactor and S-adenosylmethionine, or SAMe, as a methyl donor. Variants in the VDR gene can change how well your body uses vitamin D and can indirectly increase demand on the BH4 Cycle and the Methylation Pathway.

How VDR Affects the BH4 Cycle and Methylation Pathway

Active VDR signaling promotes the expression of enzymes involved in dopamine and serotonin synthesis. When VDR activity is reduced, the efficiency of these pathways can decline. That can lead to lower neurotransmitter production and place extra biochemical strain on BH4 regeneration and methylation processes. Maintaining adequate vitamin D status and supporting the BH4 and methylation pathways can help preserve cognitive and emotional wellness.

Testing and Monitoring

  • Consider a 25-hydroxyvitamin D blood test to check vitamin D status.
  • Review basic metabolic labs with your healthcare provider, including magnesium and B vitamin status, if neurotransmitter balance or mood concerns exist.
  • Genetic results are one piece of the picture. Discuss results and next steps with a qualified healthcare professional.

Genetic Interpretations

Two effect alleles (AA at rs731236)

You carry two copies of the effect allele for rs731236. This genotype is associated with reduced VDR expression or activity. Lower VDR signaling can reduce the ability of cells to respond to vitamin D and may impair regulation of enzymes that support dopamine and serotonin synthesis. That can increase biochemical demand on BH4 regeneration and on methylation pathways that supply SAMe. People with this genotype may be more sensitive to low vitamin D status and may benefit from more attentive vitamin D testing and support.

  • Possible effects: reduced neurotransmitter synthesis, greater need for BH4 and methyl donors, increased sensitivity to low vitamin D.
  • Practical considerations: confirm vitamin D levels, consider optimized vitamin D intake under medical supervision, support methylation and BH4 pathways.
One effect allele (AG at rs731236)

You carry one copy of the effect allele. This may moderately reduce VDR expression or activity compared with the noncarrier genotype. Partial reduction in VDR function can subtly influence neurotransmitter production and immune signaling, potentially contributing to mild imbalances in the BH4 Cycle and the Methylation Pathway. You may have a slightly increased need for consistent vitamin D status and targeted nutritional support to maintain neurotransmitter balance.

  • Possible effects: mild reduction in VDR signaling, modest impact on dopamine and serotonin production, increased need for consistent vitamin D.
  • Practical considerations: monitor vitamin D, maintain dietary and lifestyle supports for methylation and BH4 pathways.
No effect alleles (GG at rs731236)

You do not carry the effect allele. This genotype is generally associated with normal VDR expression and function, which supports effective vitamin D signaling. Normal VDR activity helps maintain balanced neurotransmitter production and immune function and reduces the likelihood of disturbances to the BH4 Cycle and Methylation Pathway related to VDR function. Routine attention to vitamin D status and general nutritional health is still important for overall wellness.

  • Possible effects: standard VDR signaling, reduced genetic risk from rs731236 for VDR-related neurotransmitter imbalance.
  • Practical considerations: follow general recommendations for adequate vitamin D, diet, and lifestyle to support mental and metabolic health.

Diet and Nutrition Recommendations

  • Vitamin D sources: aim for safe sun exposure and include dietary vitamin D sources such as fatty fish, egg yolks, and fortified foods. Supplementation with vitamin D3 may be considered if levels are low.
  • Support BH4 and neurotransmitter synthesis: include adequate protein with tyrosine and phenylalanine from lean meats, dairy, eggs, legumes, and nuts. These amino acids are precursors for neurotransmitter production.
  • Methylation support: eat folate-rich vegetables (leafy greens, asparagus, Brussels sprouts), B12 sources (fish, meat, dairy or supplement if needed), and B6 containing foods (chicken, bananas, potatoes).
  • Magnesium and cofactors: include magnesium-rich foods such as nuts, seeds, whole grains, and leafy greens to support enzymatic reactions that depend on magnesium.
  • Balanced diet: focus on whole foods, limit highly processed foods and excess sugar, and maintain regular meal timing to support metabolic balance.

Supplement Recommendations (Educational Only)

  • Vitamin D3: consider supplementing if blood 25-hydroxyvitamin D is below optimal range. Dosing should be individualized and managed with your healthcare provider.
  • Vitamin K2 and magnesium: these may be paired with vitamin D3 to support calcium metabolism and enzymatic function, respectively.
  • Methylation cofactors: methylfolate, methylcobalamin (B12), and pyridoxal-5-phosphate (B6) can support methylation reactions if a clinical need exists. Use under healthcare guidance.
  • BH4 pathway supports: in some situations, L-tyrosine or specific clinical-grade supports that target BH4 function are used. Only take under provider direction.
  • Avoid high dose self-prescribing without medical oversight. Supplements can interact with medications and underlying conditions.

Lifestyle Recommendations

  • Sunlight exposure: get regular, safe sun exposure to support natural vitamin D production. Adjust timing and duration for skin type and geographic location.
  • Sleep and stress: prioritize 7 to 9 hours of sleep and practice stress reduction techniques such as mindfulness, breathing exercises, or regular physical activity. Chronic stress can increase demand on neurotransmitter synthesis and methylation.
  • Regular exercise: moderate aerobic activity and resistance training support mood, neurotransmitter balance, and metabolic health.
  • Limit alcohol and smoking: both can impair methylation and nutrient absorption and may worsen neurotransmitter balance.

When to Talk with Your Healthcare Provider

  • If you have symptoms of mood disturbance, fatigue, or cognitive changes discuss these with your provider and consider targeted labs.
  • Before starting supplements such as vitamin D3, methylfolate, B12, or others, consult your healthcare provider to tailor dosing and screen for interactions.
  • If you have complex health concerns or are on medications that affect mood or metabolism, seek professional guidance for an integrated plan.

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice. Always consult your healthcare provider before making changes to diet, supplements, medications, or lifestyle based on genetic results.