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Vitamin D status varies considerably between individuals, even among people with similar diets, sunlight exposure, and supplementation habits. While environmental and lifestyle factors clearly influence circulating vitamin D concentrations, genetic variation also contributes to these differences. The vitamin D receptor (VDR) is of particular interest because it mediates the biological actions of active vitamin D and connects vitamin D metabolism with downstream cellular signaling. Research on VDR polymorphisms has therefore provided valuable insight into why individuals may differ in their 25-hydroxyvitamin D [25(OH)D] status and vitamin D-related biological responses.
25(OH)D is the principal circulating biomarker used to assess vitamin D status. Vitamin D obtained through sunlight exposure, dietary sources, or supplementation is initially hydroxylated in the liver, primarily by enzymes such as CYP2R1 and CYP27A1, to produce 25(OH)D. It is subsequently converted to the biologically active hormone 1,25-dihydroxyvitamin D [1,25(OH)₂D], which binds to VDR and regulates gene transcription. The VDR gene is located on chromosome 12q13.1, and extensive genetic variation has been identified within this locus. Because VDR controls cellular responses to active vitamin D, variations in this receptor may influence vitamin D signaling and, in some populations, may also be associated with differences in circulating 25(OH)D concentrations.
Four VDR polymorphisms have been investigated particularly extensively: FokI (rs10735810), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236). FokI is located near the VDR translation initiation region and can affect the resulting VDR protein structure, whereas BsmI, ApaI, and TaqI are commonly classified as synonymous or silent variants. Although these variants may not directly change the amino acid sequence, they should not automatically be considered biologically irrelevant because genetic changes in these regions may influence transcript behavior or may be inherited together with functional variants. BsmI, ApaI, and TaqI are also relatively closely located within the VDR region, making linkage disequilibrium an important consideration when interpreting associations between these polymorphisms and vitamin D-related traits.
TaqI (rs731236) has been frequently examined in studies investigating the relationship between VDR genetics and circulating 25(OH)D. Some research has identified significant genotype-dependent differences in serum 25(OH)D, with TT carriers showing higher concentrations in certain populations, while the T allele has also been associated with higher 25(OH)D and lower BMI in specific cohorts. Other investigations have reported associations between particular rs731236 genotypes and lower vitamin D status. For example, research in a Greek population found that the Tt genotype was associated with an increased likelihood of having 25(OH)D below 30 ng/mL, with an odds ratio of 3.56, while the tt genotype was also associated with increased risk. These differences demonstrate that the relationship between TaqI and vitamin D status is population-dependent rather than universally predictable.
BsmI (rs1544410) has also been associated with vitamin D status in some populations, with the b allele linked to lower 25(OH)D concentrations or an increased likelihood of vitamin D insufficiency in certain studies. FokI provides another potentially important mechanism because it can influence the structure of the VDR protein itself. In one twin study, individuals homozygous for the shorter VDR protein form had mean 25(OH)D concentrations of approximately 25.8 ± 2.2 ng/mL, compared with 33.3 ± 1.6 ng/mL in individuals carrying the longer VDR protein form. Although these observations support a relationship between VDR genetic variation and vitamin D status, they do not mean that either BsmI or FokI alone determines an individual's vitamin D concentration, which is influenced by multiple genetic and environmental factors.
Research has increasingly examined VDR variants beyond the four classic polymorphisms, revealing a more complex genetic architecture. A study in a Brazilian population identified six variants—rs7967152, rs9729, rs793837, rs11168287, rs7963776, and rs4237855—that were associated with a lower risk of vitamin D insufficiency, while rs59128934, rs7965274, and rs2853564 were associated with an increased risk. These findings suggest that VDR-related effects may involve multiple genetic sites rather than a single dominant polymorphism. They also highlight the importance of population-specific genetic backgrounds when interpreting genetic associations, because allele frequencies, linkage patterns, and interactions with environmental exposures can differ substantially between populations.
The genetic regulation of 25(OH)D status extends well beyond VDR. GC, which encodes vitamin D–binding protein, influences the transport and distribution of vitamin D metabolites, while CYP2R1 and CYP27A1 participate in the formation of 25(OH)D and CYP27B1 contributes to the production of active 1,25(OH)₂D. CYP24A1 is involved in vitamin D catabolism, and variants in NADSYN1/DHCR7 have also been associated with circulating vitamin D concentrations. In this broader pathway, VDR primarily influences vitamin D signal transduction, whereas other genes affect vitamin D synthesis, hydroxylation, transport, activation, or degradation. The resulting 25(OH)D concentration therefore reflects the combined effects of multiple biological processes.
Studies of families and twins indicate that genetic factors can make a substantial contribution to differences in circulating 25(OH)D, although estimates vary considerably depending on the population and study design. Reported genetic contributions have ranged from approximately 23–43% to 77–80% in different investigations. These estimates should not be interpreted as evidence that vitamin D status is genetically predetermined. Instead, they indicate that inherited differences can contribute to population-level variation while environmental factors—including latitude, season, sunlight exposure, dietary intake, supplementation, BMI, age, and lifestyle—continue to exert major effects. A VDR genotype associated with lower 25(OH)D in one population therefore does not necessarily predict vitamin D deficiency in every individual.
Differences between populations are one of the major challenges in interpreting VDR polymorphism studies. The same allele may be associated with higher 25(OH)D in one population but show no significant association or even an opposite relationship in another. Linkage disequilibrium is one possible explanation, particularly for BsmI, ApaI, and TaqI, because these variants may act as genetic markers for nearby functional variants whose frequency and inheritance patterns differ among populations. Environmental factors further complicate the picture because sunlight exposure, season, diet, supplementation, body composition, and other lifestyle characteristics can modify the relationship between genotype and circulating 25(OH)D. Consequently, genetic findings should be interpreted within their specific population and environmental context rather than treated as universally applicable rules.
The evidence accumulated to date supports the view that VDR genetic polymorphisms are among the genetic factors that can influence 25(OH)D status, particularly variants such as FokI, BsmI, ApaI, and TaqI. However, their effects are generally modest and context-dependent rather than deterministic. Genetic testing alone cannot replace direct measurement of circulating 25(OH)D when evaluating vitamin D status, but VDR genotyping can provide useful research insights into inter-individual differences in vitamin D signaling and metabolism. For researchers investigating vitamin D biology, considering VDR variation alongside genes such as GC, CYP2R1, CYP27B1, and CYP24A1 can provide a more complete picture of the biological factors underlying differences in vitamin D status.
VDR polymorphisms illustrate how genetic variation can interact with nutritional and environmental factors to shape vitamin D physiology. Although FokI, BsmI, ApaI, and TaqI remain among the most extensively studied VDR variants, current evidence suggests that the relationship between genotype and 25(OH)D is considerably more complex than a single genetic marker determining vitamin D status. Differences in genetic background, linkage disequilibrium, sunlight exposure, diet, BMI, and other environmental conditions can all modify the observed association. Understanding these interactions may ultimately help researchers move toward a more individualized view of vitamin D biology, in which circulating 25(OH)D measurements and genetic information are considered together rather than in isolation.
Yes. Variants in the VDR gene, particularly FokI, BsmI, ApaI, and TaqI, have been associated with differences in circulating 25(OH)D concentrations in some populations. However, the direction and strength of these associations can vary between populations.
The four most extensively studied VDR polymorphisms are FokI (rs10735810), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236). These variants have been investigated for their potential relationships with vitamin D status, metabolic traits, immune function, and other vitamin D–related outcomes.
Not necessarily. A VDR polymorphism may contribute to differences in vitamin D status, but it does not independently determine whether someone will become vitamin D deficient. Sunlight exposure, dietary intake, supplementation, BMI, age, season, geographic location, and other genetic factors can all influence circulating 25(OH)D.
Differences may result from linkage disequilibrium, genetic background, allele frequencies, and environmental factors. For example, BsmI, ApaI, and TaqI may act as markers for nearby functional variants, and their genetic relationships can differ between populations. Differences in sunlight exposure, diet, and lifestyle can further modify the observed association.
VDR genotyping can be valuable for research into individual differences in vitamin D metabolism and signaling, but it should not replace direct measurement of circulating 25(OH)D. Vitamin D status is determined by multiple genetic and environmental factors, so combining genetic information with biochemical 25(OH)D measurements provides a more comprehensive assessment.
References
| Target | Cat. No. | Product Name | Host | Application | |
| 25-OH Vitamin D | DMABA-JX119 | Rabbit Anti-25 OH Vitamin D monoclonal antibody, clone S594L4 | Rabbit | ELISA, LFIA, CLIA | Inquiry |
| DMABA-JX120 | Rabbit Anti-25 OH Vitamin D monoclonal antibody, clone S595K5 | Rabbit | ELISA, LFIA, CLIA | Inquiry | |
| DMAB-JXL2399 | Goat Anti-25-OH VD2/VD3 Monoclonal Antibody, clone 5C3 | CHO | ELISA, CLIA, LFIA | Inquiry | |
| DMAB2913 | Mouse Anti-25 OH Vitamin D3 monoclonal antibody, clone L35235N | Mouse | ELISA | Inquiry | |
| DMAB2914 | Mouse Anti-25 OH Vitamin D3 Monoclonal antibody, clone C2531M | Mouse | ELISA | Inquiry | |
| CABT-L1343W | Humanized Anti-Human 25-OH-VD Monoclonal antibody, clone 214I2T | Humanized | LFIA, CLIA | Inquiry | |
| CABT-L1344W | Humanized Anti-Human 25-OH-VD Monoclonal antibody, clone 214I5 | Humanized | PETIA | Inquiry |
| Target | Cat. No. | Product Name | Conjugate | Application | |
| 25-OH Vitamin D | DAG-WT2678 | 25-hydroxyvitamin D control | Unconjugated | Calibration, Control | Inquiry |
| DAG-WT2679 | 25-hydroxyvitamin D2 control | Unconjugated | Calibration, Control | Inquiry | |
| DAG-WT2680 | 25-hydroxyvitamin D3 control | Unconjugated | Calibration, Control | Inquiry | |
| DAG03219 | 25-OH Vitamin D3 [BSA] | BSA | ELISA, LFIA | Inquiry | |
| DAGA-126H | 25-OH Vitamin D [HRP] | HRP | ELISA | Inquiry | |
| DAGA-126K | 25-OH Vitamin D [KLH] | KLH | Immunogen | Inquiry | |
| DAG-WT6032B | 25-OH Vitamin D2 [BSA] | BSA | ELISA, LFIA | Inquiry |
| Target | Cat. No. | Product Name | Species Reactivity | Application | Detection Sample | |
| 25-OH Vitamin D | DEIA4458 | 25-OH Vitamin D ELISA Kit | Human | Quantitative | Serum, Plasma | Inquiry |
| DEIA1733 | 25 (OH) Vitamin D ELISA Kit | Human | Quantitative | plasma, serum | Inquiry | |
| DEIA002J | 25-OH Vitamin D direct (1-point calibration) ELISA Kit | Human | Quantitative | serum | Inquiry | |
| DEIA003J | 25-OH Vitamin D direct day ELISA Kit | Human | Quantitative | serum, fresh plasma | Inquiry | |
| DEIA004J | 25-OH Vitamin D direct ELISA Kit | Human | Quantitative | serum, fresh plasma | Inquiry | |
| DEIA005J | 25-OH Vitamin D Xpress ELISA Kit | Human | Quantitative | serum, fresh EDTA plasma | Inquiry | |
| DEIA006J | 25-OH Vitamin D ELISA Kit | Human | Quantitative | serum, plasma | Inquiry | |
| DEIA2219 | 25-OH Vitamin D (total) ELISA Kit | Human | Quantitative | Serum | Inquiry | |
| DEIA-BJ574-1 | Human 25 (OH) D3 ELISA kit | Human | Quantitative | Serum, plasma and other biological fluids. | Inquiry | |
| DEIA-BJ2145 | Rat 25 Hydroxy Vitamin D3 ELISA Kit | Rat | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | |
| DEIA-NS2651 | 25OH-D (Total 25-OH Vitamin D) ELISA Kit | Universal | Quantitative | Serum, plasma, cellculture supernatant and other biological samples. | Inquiry | |
| DEIA-BJ648 | Human 25 Hydroxy Vitamin D ELISA kit | Human | Quantitative | biological fluids. | Inquiry |
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