rs1544410 — VDR BsmI

VDR BsmI — How Your Cells Respond to Vitamin D

The vitamin D receptor (VDR) is a nuclear receptor ¹¹ A nuclear receptor is a protein that binds hormones or vitamins inside the cell and directly regulates gene expression that mediates the biological effects of vitamin D throughout your body. When active vitamin D (calcitriol) ²² Calcitriol (1,25-dihydroxyvitamin D) is the hormonally active form of vitamin D binds to VDR, it triggers gene expression changes that affect calcium absorption, immune function, cell growth, and hundreds of other processes. VDR is expressed in nearly every tissue in the body, which is why vitamin D affects so many aspects of health.

The Mechanism

The BsmI variant (rs1544410) is located in an intronic region of the VDR gene. While it does not directly change the protein sequence, it is in linkage disequilibrium ³³ Linkage disequilibrium: nearby genetic variants that are inherited together more often than expected by chance with functional variants that affect VDR mRNA stability and expression levels. The T allele is associated with reduced VDR expression, meaning your cells produce fewer vitamin D receptors and are therefore less responsive to circulating vitamin D. The variant frequency varies dramatically by ancestry — 40% in Europeans but only 6% in East Asians.

The Evidence

A meta-analysis of 26 studies⁴⁴ meta-analysis of 26 studies
Tao S et al. VDR BsmI polymorphism and osteoporosis risk, 2012 and a larger 42-study meta-analysis⁵⁵ larger 42-study meta-analysis
Zhao L et al. VDR BsmI and osteoporosis in postmenopausal women, 2020 found that VDR BsmI variants are associated with osteoporosis susceptibility in Caucasians (OR 0.70 for bb vs BB), bone mineral density, and calcium absorption efficiency. The associations are strongest in populations with lower baseline vitamin D levels. Additional research has linked VDR variants to immune function, autoimmune disease risk, and cancer susceptibility, though these associations are more complex and context-dependent.

The Vitamin D Optimization Challenge

VDR variants create a situation where standard blood levels of vitamin D may not produce standard biological effects. If your cells have fewer vitamin D receptors, you may need higher circulating vitamin D levels to achieve the same cellular response as someone with normal VDR expression. This is why some people with "adequate" blood levels still seem to benefit from higher vitamin D intake.

Practical Implications

If you carry the T allele, maintaining vitamin D levels in the optimal range (30-50 ng/mL) is important, and you may benefit from aiming toward the higher end of that range. Regular testing (1-2 times per year) helps you calibrate your supplementation. Vitamin D3 is preferred over D2, and taking it with a fat-containing meal improves absorption.

Interactions

VDR interacts with CYP2R1 (rs10741657) — if both vitamin D activation and receptor sensitivity are impaired, the combined "double hit" significantly impacts vitamin D status.