# VDR — Vitamin D receptor
URL: https://genohealth.app/genes/vdr
Category: Vitamins & minerals
Chromosome: 12q13.11
Key variants: rs1544410 (BsmI), rs731236 (TaqI), rs2228570 (FokI)
Last reviewed: 2026-04-25

## Summary
VDR encodes the receptor that vitamin D binds to. Variants like FokI (rs2228570), BsmI (rs1544410) and TaqI (rs731236) influence how efficiently your body uses vitamin D for bone, immune and metabolic health — even when blood D levels look normal.

## What it does
Once vitamin D is hydroxylated to calcitriol (1,25-(OH)2-D), it binds the vitamin D receptor (VDR) inside cells. The activated VDR translocates to the nucleus and regulates the expression of >1,000 genes involved in calcium absorption, bone remodeling, innate and adaptive immunity, insulin sensitivity, and inflammation control.

## Why it matters
Less efficient VDR variants are linked to lower bone mineral density, weaker antimicrobial immune response, higher autoimmune risk (MS, type 1 diabetes, Hashimoto's), and worse outcomes in respiratory infections — even when serum 25(OH)D is in the normal range. Many people with VDR variants need higher D3 dosing or D3+K2 combinations to reach functional adequacy.

## Variants
- rs2228570 (FokI (C→T, Met1Thr)) — risk allele T (f allele); T allele produces a longer, less active receptor protein. (frequency: T allele ≈35% globally)
- rs1544410 (BsmI (G→A)) — risk allele A (b allele); Intronic; affects mRNA stability; A allele linked to lower BMD in some populations. (frequency: A allele ≈40%)
- rs731236 (TaqI (T→C)) — risk allele C (t allele); Synonymous; in linkage with BsmI. (frequency: C allele ≈40%)
- rs7975232 (ApaI) — risk allele n/a; Often co-reported with BsmI/TaqI haplotype. (frequency: ≈50%)

## Genotypes
- **FokI CC (FF)** (~40%): Most active receptor isoform. → Standard vitamin D guidance; aim 25(OH)D 30-50 ng/mL.
- **FokI CT or TT (Ff/ff)** (~60%): Less active receptor. → May need higher D3 dose to reach 40-60 ng/mL; pair with K2 and magnesium.
- **BsmI/TaqI variant haplotype** (n/a): Lower BMD risk in some studies. → Prioritize weight-bearing exercise, calcium intake and adequate D3.

## Conditions
- **Osteoporosis** — Increased risk: VDR variants modestly increase fracture risk; effect amplified by low D and inadequate calcium.
- **Multiple sclerosis** — Increased risk: Low D + VDR variants associated with MS risk and severity.
- **Type 1 diabetes** — Increased risk: Childhood D deficiency + VDR variants increase risk.
- **Respiratory infections** — Increased severity risk: Inadequate D + VDR variants linked to worse outcomes in flu, RSV and COVID-19.
- **Hashimoto's thyroiditis** — Increased risk: VDR variants overrepresented in autoimmune thyroid disease.

## Diet
Rationale: Diet alone rarely provides enough D; the priority is ensuring cofactors (magnesium, K2, calcium) needed to convert and use supplemental D effectively.
Prioritize: Fatty fish (salmon, sardines, mackerel) 2-3x/week; Egg yolks (pasture-raised); Mushrooms exposed to UV; Calcium from leafy greens, sardines, dairy; Magnesium-rich foods (pumpkin seeds, dark chocolate)
Limit: Excess phytate from raw bran (binds calcium); Heavy alcohol (impairs D activation)

## Lifestyle
- Test serum 25(OH)D twice a year — winter trough and summer peak.
- Get 15-20 minutes of midday sun on bare arms several times per week (May-September at temperate latitudes).
- Weight-bearing exercise 3x/week — required to translate D into bone density.
- Avoid prolonged glucocorticoid use without bone monitoring.

## Supplements
- **Vitamin D3 (cholecalciferol)** — 2000-5000 IU/day, titrated to 25(OH)D 40-60 ng/mL, form: D3, not D2. Higher doses (>4000 IU) for VDR-variant carriers; retest after 8-12 weeks.
- **Vitamin K2 (MK-7)** — 100-200 mcg/day, form: MK-7 (longer half-life than MK-4). Routes calcium to bone, away from arteries; essential when supplementing D long-term.
- **Magnesium glycinate** — 200-400 mg/day, form: Glycinate, malate or threonate. Required for vitamin D activation; deficiency mimics D deficiency.
- **Calcium (food first)** — 1000-1200 mg total/day from food + supplement if needed, form: Calcium citrate if supplementing. Avoid mega-dose calcium supplements; food sources are safer.
- **Boron** — 3-6 mg/day, form: Boron glycinate. Modestly raises calcitriol and supports bone matrix.

## Contraindications
- High-dose D3 (>5000 IU/day) without testing — risk of hypercalcemia.
- D3 supplementation without K2 long-term — may contribute to vascular calcification.
- Granulomatous diseases (sarcoidosis, TB) — endogenous D activation can cause hypercalcemia; specialist supervision required.

## FAQ
**Q: How much vitamin D should I take with VDR variants?**
A: There is no single dose — your serum 25(OH)D level is the target. Many VDR-variant carriers need 4,000-5,000 IU/day to reach 40-60 ng/mL. Test after 8-12 weeks and adjust. Always pair with K2 and magnesium.

**Q: What is the best form of vitamin D?**
A: Vitamin D3 (cholecalciferol) raises 25(OH)D more effectively than D2. Liquid or softgel forms are well absorbed; take with a fat-containing meal.

**Q: Do I need vitamin K2 with D3?**
A: If you take D3 daily long-term, yes. K2 (MK-7, 100-200 mcg) directs calcium to bone and away from arteries. The combination is especially important for VDR-variant carriers needing higher D3 doses.

**Q: Why is my vitamin D still low even with supplements?**
A: Three common reasons: (1) magnesium deficiency blocks D activation, (2) gut malabsorption (celiac, IBD), (3) obesity sequesters D in adipose tissue. VDR variants alone rarely cause refractory low D.

**Q: Are VDR variants linked to autoimmune disease?**
A: Yes — modestly. VDR variants are overrepresented in MS, type 1 diabetes and Hashimoto's. Maintaining 25(OH)D 40-60 ng/mL is a reasonable goal, though it does not guarantee prevention.

## Citations
- Uitterlinden et al., Gene 2004 (PMID 15315808): Comprehensive review of VDR polymorphisms and disease associations.
- Holick, NEJM 2007 (PMID 17634462): Foundational vitamin D deficiency review; clinical thresholds and dosing.
- Martineau et al., BMJ 2017 (PMID 28202713): Meta-analysis: D3 supplementation reduces acute respiratory infection risk, more in deficient subjects.

Disclaimer: Informational only — not medical advice.