VDR Cdx2 (rs11568820): Vitamin D Receptor

The VDR gene encodes the Vitamin D Receptor, a nuclear receptor that mediates vitamin D's effects throughout the body. The Cdx2 polymorphism (rs11568820) is located in the promoter region and affects how much VDR your intestinal cells produce, influencing calcium absorption, bone health, immune function, and skin health.

Understanding the Vitamin D Receptor

The VDR is a nuclear receptor that, when activated by vitamin D, regulates hundreds of genes:

• Calcium homeostasis: Controls intestinal calcium absorption
• Bone metabolism: Regulates osteoblast and osteoclast function
• Immune function: Modulates both innate and adaptive immunity
• Skin health: Affects keratinocyte proliferation and differentiation
• Cell growth: Influences cell cycle and cancer prevention

The Cdx2 Binding Site

Cdx2 is a transcription factor particularly active in intestinal cells:

• Location: VDR gene promoter region
• Function: Controls VDR expression in the intestine
• Impact: Affects how much VDR is available to respond to vitamin D

Understanding Your Genotype

• G/G: Lower VDR transcription in intestine
• G/A: Intermediate VDR expression
• A/A: Higher VDR transcription - better Cdx2 binding

The A allele creates a more active Cdx2 binding site, leading to increased VDR expression and potentially better vitamin D response.

Calcium Absorption Effects

Intestinal Absorption

• VDR in intestinal cells is crucial for calcium absorption
• A allele carriers may absorb calcium more efficiently
• G/G genotype may need higher vitamin D to achieve same absorption
• Particularly relevant for bone health and osteoporosis prevention

Research Findings

• The A allele associated with higher bone mineral density in some studies
• May protect against fractures in elderly populations
• Effects most pronounced when vitamin D status is marginal

Skin Health Implications

Vitamin D and its receptor have important roles in skin:

Keratinocyte Function

• VDR regulates skin cell proliferation and differentiation
• Important for skin barrier function
• Affects wound healing
• Influences skin immune responses

Skin Conditions

• Psoriasis: VDR variants may influence severity and treatment response
• Eczema: Vitamin D/VDR affects skin barrier and inflammation
• Skin aging: Adequate vitamin D signaling supports skin health
• Wound healing: VDR activation promotes repair

Sun Exposure Paradox

For skin health, there's a balance:

• Some sun exposure needed for vitamin D synthesis
• Excess UV causes skin damage and cancer risk
• Those with lower VDR expression (G/G) may benefit more from supplementation to avoid excess sun exposure

Immune Function

VDR plays important roles in immunity:

Innate Immunity

• Vitamin D/VDR induces antimicrobial peptides (cathelicidin)
• Important for defense against infections
• May influence susceptibility to respiratory infections

Autoimmune Conditions

• VDR variants associated with autoimmune disease risk
• Multiple sclerosis, type 1 diabetes, rheumatoid arthritis links
• Vitamin D is immunomodulatory - balances immune response

Optimizing Vitamin D Status

For G/G Genotype (Lower VDR)

May need more attention to vitamin D optimization:

• Regular vitamin D level testing (25-hydroxyvitamin D)
• Potentially higher supplementation needs
• Target higher end of optimal range (40-60 ng/mL)
• Ensure adequate calcium intake alongside vitamin D

Vitamin D Sources

• Sunlight: UVB exposure (moderate, avoiding burns)
• Fatty fish: Salmon, mackerel, sardines
• Fortified foods: Milk, cereals, orange juice
• Supplements: D3 (cholecalciferol) preferred over D2
• Cod liver oil: Traditional vitamin D source

Vitamin D Supplementation

• Common doses: 1,000-5,000 IU daily for adults
• Take with fat for absorption
• Test levels to guide dosing
• Consider K2 alongside D3 for bone health

Prevalence

• A allele frequency: Approximately 20-25% in European populations
• Population variation: Differs across ancestries
• Clinical significance: Most relevant when vitamin D status is suboptimal

VDR Variant Interactions

Multiple VDR variants affect function:

• Cdx2 (rs11568820): Affects intestinal VDR expression
• FokI (rs2228570): Affects VDR protein structure
• BsmI (rs1544410): Associated with VDR mRNA stability

Analyzing all VDR variants together gives the most complete picture of your vitamin D genetics.

Testing with NutraHacker

NutraHacker's Skincare Panel analyzes multiple VDR variants, helping you understand your vitamin D genetics and optimize supplementation for skin and overall health.

Frequently Asked Questions

If I have G/G, do I need more vitamin D?

Potentially. The G/G genotype is associated with lower VDR expression, which may mean you need higher vitamin D levels to achieve the same biological effects. Regular testing of your 25-hydroxyvitamin D levels and adjusting supplementation accordingly is the best approach.

Does this affect my skin directly?

Yes. VDR is expressed in skin cells and regulates their function. Lower VDR expression may affect skin barrier function, wound healing, and potentially skin aging. Optimizing your vitamin D status can support healthy skin regardless of genotype.

Should I get more sun exposure if I have the G/G variant?

Not necessarily more than recommended. While sun exposure creates vitamin D, excess UV damages skin and increases cancer risk. For G/G carriers, supplementation may be a safer way to optimize vitamin D than increasing sun exposure. Always use sun protection.

References

1. Arai H, et al. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density. J Bone Miner Res. 1997;12(6):915-921.
2. Bikle DD. Vitamin D and the skin: Physiology and pathophysiology. Rev Endocr Metab Disord. 2012;13(1):3-19.
3. Fang Y, et al. Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to Crohn's disease. Gut. 2003;52(12):1698-1703.