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QDPR (rs1031326): How your genotype influences BH4 recycling, neurotransmitters, and nitric oxide

The QDPR gene encodes quinoid dihydropteridine reductase (DHPR), the enzyme that recycles BH2 back into BH4. BH4 is an essential cofactor for enzymes that make dopamine, serotonin, melatonin, norepinephrine, and nitric oxide. When QDPR activity is reduced, BH4 recycling becomes less efficient, which can lower neurotransmitter and nitric oxide production and increase oxidative stress. These changes can affect mood, cognition, vascular tone, and immune signaling. QDPR function also interacts with methylation and folate biology (for example MTHFR and 5-MTHF), so combined genetic or nutritional factors can amplify effects.

What this means for health and wellness

  • Lower BH4 availability can reduce synthesis of neurotransmitters affecting mood, sleep, motivation, and cognitive function.
  • Reduced nitric oxide production can affect blood vessel health, blood flow, and aspects of the urea cycle.
  • Compensation through methylation pathways may increase demand for 5-MTHF and other methylation cofactors.
  • Oxidative stress can rise if BH4 recycling is impaired, increasing need for antioxidant support.

Practical takeaways

  • Consider supporting BH4-dependent systems through targeted diet, lifestyle, and selective supplements.
  • Check related genes and biomarkers (MTHFR, COMT, CBS, homocysteine, folate status) to prioritize interventions.
  • Work with your healthcare provider before starting supplements, changing medications, or treating health conditions. PlexusDx does not provide medical advice. Always consult your healthcare provider about test results and treatment decisions.

Genetic interpretation by genotype

Two effect alleles (CC) — higher likelihood of reduced QDPR activity

If you have the CC genotype for rs1031326, you carry two copies of the effect allele. This is associated with reduced QDPR enzyme activity and a decreased ability to recycle BH2 into BH4. Expected consequences include:

  • Lower BH4 availability for neurotransmitter synthesis (serotonin, dopamine, melatonin, norepinephrine).
  • Potential for mood instability, reduced motivation, sleep dysregulation, and cognitive difficulties in some people.
  • Lower nitric oxide production, which can affect vascular tone and exercise tolerance.
  • Increased reliance on methylation pathways and potential vulnerability when 5-MTHF is low or when MTHFR variants are present.

Recommended actions

  • Blood tests to consider: plasma folate (including 5-MTHF if available), homocysteine, vitamin B12, amino acids (phenylalanine, tyrosine), and markers of oxidative stress as guided by your clinician.
  • Diet: emphasize folate-rich leafy greens, whole foods with protein to supply phenylalanine and tyrosine, and nitrate-rich vegetables (beets, spinach) to support nitric oxide.
  • Supplements to discuss with your provider: active folate (5-MTHF) if low or with MTHFR variants; methylcobalamin (B12) if indicated; BH4 support strategies such as sapropterin only under medical supervision; antioxidants (vitamin C, N-acetylcysteine, glutathione precursors); magnesium; and a balanced multivitamin. Start low and monitor response.
  • Lifestyle: regular aerobic exercise to stimulate nitric oxide and neurotransmitter balance, stress management (sleep hygiene, mindfulness), avoid smoking and excessive alcohol, and support gut health to aid neurotransmitter precursors.
One effect allele (CT) — mildly reduced QDPR activity

If you have the CT genotype for rs1031326, you carry one effect allele and one non-effect allele. This associates with a modest reduction in QDPR activity. Many people with this genotype function normally, but under stressors or with other genetic or nutritional hits, BH4-dependent processes may be strained.

  • Watch for subtle changes in mood, energy, sleep, or exercise tolerance under stress or illness.
  • Potential increased requirement for methylation and antioxidant support when combined with MTHFR, COMT, or CBS variants.

Recommended actions

  • Consider baseline labs: folate, B12, homocysteine. Track symptoms and lifestyle factors that increase oxidative demand.
  • Diet: prioritize balanced protein intake, leafy greens for folate, and foods high in vitamin C to support BH4 stability.
  • Supplements to discuss: low-dose 5-MTHF if levels are low or if MTHFR variants exist; antioxidants such as vitamin C and alpha-lipoic acid; consider magnesium and B12 if deficient.
  • Lifestyle: maintain regular exercise, prioritize sleep, and minimize chronic stressors to reduce BH4 oxidation.
Zero effect alleles (TT) — typical QDPR function

If you have the TT genotype for rs1031326, you carry two non-effect alleles and are generally associated with normal QDPR enzyme activity. BH4 recycling is typically efficient, supporting balanced neurotransmitter and nitric oxide production. This reduces strain on methylation pathways under normal conditions.

  • Continue to support overall health with a nutrient-dense diet, good sleep, and stress management.
  • Routine monitoring of folate and B12 is reasonable if symptoms or other risk factors arise.

Recommended actions

  • Diet: maintain varied whole-food intake with adequate protein and plentiful vegetables, especially leafy greens and nitrate-rich produce.
  • Supplements: generally not required for QDPR support unless lab results or symptoms indicate deficiency. Use 5-MTHF or B12 only as clinically indicated.
  • Lifestyle: continue exercise, sleep hygiene, and antioxidant-rich foods to preserve BH4 and overall metabolic resilience.

General diet, supplement, and lifestyle guidance

  • Diet: focus on leafy greens (folate), high-quality protein (phenylalanine and tyrosine precursors), nitrate-rich vegetables (support nitric oxide), vitamin C rich fruits and vegetables, omega-3 fats, and antioxidant-rich foods (berries, cruciferous vegetables).
  • Supplements to discuss with your provider: active folate (5-MTHF) when folate status is low or with MTHFR variants, methylcobalamin (B12) if low, vitamin C as an antioxidant to protect BH4, N-acetylcysteine or glutathione precursor support for oxidative stress, magnesium, and a balanced multivitamin. BH4 analogs or prescription BH4 should only be used under specialist supervision.
  • Lifestyle: regular aerobic and resistance exercise, consistent sleep schedule, stress reduction techniques (meditation, breathing practices), avoid smoking and excessive alcohol, and support gut health to assist precursor absorption and neurotransmitter balance.
  • Monitor and collaborate: check homocysteine, folate, and B12 levels with your clinician, and discuss genetic interactions (MTHFR, COMT, CBS) that may change priorities.

Important note

PlexusDx provides education about genetic predispositions only. This information is not medical advice and is not a substitute for consultation with a qualified healthcare professional. Always discuss genetic results, tests, medications, supplements, and treatment options with your healthcare provider to determine what is appropriate for your health situation.