Two people take the same vitamin D supplement for a year. One reaches a comfortable blood level, the other stays low. Part of the explanation lies in a gene called GC, and a randomized trial published in July 2026 in Frontiers in Nutrition puts numbers on it.
GC, the vitamin D carrier
The GC gene makes vitamin D binding protein, which carries most of the vitamin D circulating in your blood. Common variants of GC, such as rs7041 and rs2282679, change the amount and the form of this protein. In large population studies they are among the variants most strongly linked to the blood level of 25-hydroxyvitamin D, or 25(OH)D, the marker your doctor measures.
The trial
The team (Alonso, Ralston and colleagues, Medical University of Graz and University of Edinburgh) used data from VDOP, a trial run in northwest England in which 323 people over 70 took a monthly dose of vitamin D3 of 12,000, 24,000 or 48,000 IU for 12 months. They studied four variants: two in GC, one in DHCR7 and one in CYP2R1.
What they found
- Before supplementation: people with two copies of the less common version of rs7041 had the lowest levels, about 11 nmol/L below those with two common copies.
- After 12 months, at every dose: people with two common GC copies reached higher levels than those with two less common copies (table below).
- Staying below 50 nmol/L: two common copies made people roughly three times less likely to remain under this threshold, a usual definition of insufficiency (odds ratio 2.97 for rs2282679 and 2.84 for rs7041).
- DHCR7 and CYP2R1: no significant link in this trial.
| Monthly dose | rs7041: two common copies | rs7041: two less common copies |
|---|---|---|
| 12,000 IU | 62.0 nmol/L | 47.3 nmol/L |
| 24,000 IU | 68.1 nmol/L | 56.8 nmol/L |
| 48,000 IU | 82.4 nmol/L | 75.7 nmol/L |
Average 25(OH)D after 12 months of supplementation (VDOP trial, Frontiers in Nutrition, 2026). Some genotype groups were small.
What it does and does not mean
The authors are careful. They write that genotyping GC may help interpret 25(OH)D results in people who take supplements, but they do not recommend changing doses based on the gene. Researchers also still debate how much of the lower level is a real shortage: less carrier protein can mean less vitamin D measured in total without necessarily meaning less available to the tissues. And the participants were over 70 and mostly white, so the figures may differ in younger or more diverse groups.
In practice, if you carry the less common GC versions:
- Rely on a blood test, not on the dose alone. A 25(OH)D test a few months after starting or changing a supplement shows where you actually stand.
- Do not raise the dose on your own. Too much vitamin D can be harmful; adjusting it is a conversation with your doctor.
- Keep the basics: sensible sun exposure when the season allows, oily fish, eggs and fortified foods.
In your report
Fuel Your DNA reads GC (rs7041, rs4588, rs2282679), DHCR7, CYP2R1 and VDR from your raw DNA file and tells you which findings apply to you, with the food sources and the blood test worth discussing with your doctor. See the reports.
Important: this article is educational and is not medical advice. Do not start, stop or change a vitamin D supplement based on your genes alone: ask your doctor, who can check your blood level.