Can This Gene Prevent You From Burning Fat? (VDR)

The VDR gene encodes a protein called the vitamin D receptor (VDR) or calcitriol receptor. The active form of vitamin D and VDR form a complex that acts as a transcriptional factor, influencing the activity of various genes [R]. 

This complex has many biological effects, such as [R]:

• Maintaining calcium and phosphorus levels in the blood
• Regulating bone formation
• Controlling cell growth and development
• Supporting the immune system

Variations in the VDR gene have been associated with longevity and disorders such as infection, cancer, and osteoporosis [R, R, R].

Emerging research has been studying the roles of vitamin D and VDR in fat tissue, with a profound impact on metabolism and weight control [R, R].

The VDR gene encodes the vitamin D receptor. The vitamin D-VDR complex plays essential roles in bone health, immunity, metabolism, and more.

VDR in Fat Tissue: Friend or Foe?

Scientists are still figuring out the exact roles of vitamin D and VDR in the fat tissue. Activated VDR can both inhibit and support the development of fat cells, depending on other factors [R, R, R].

Interestingly, mice with over-active VDR spend less energy and become obese. On the other hand, mice lacking this receptor are leaner and have lower blood lipids. They have more active uncoupling proteins (UCPs), crucial for fat burning and energy production [R, R].

Clinical trials have confirmed the link between obesity and higher VDR expression in fat tissue. Excess VDR is associated with inflammation in fat cells, as measured by higher levels of TNF-a, IL-1b, and other cytokines [R, R, R].

VDR has complex roles in the fat tissue. Excess levels may suppress fat burning and promote inflammation, potentially contributing to weight gain.

Researchers have identified different SNPs in the VDR gene that may impact its function or activity. In this section, we will cover their association with obesity and body fat while mentioning notable limitations.

TaqI (rs731236)

When it comes to body-weight measures, TaqI or rs731236 is one of the most studied VDR variants.

Among 701 Spanish adults, those with the “A” allele had higher body weight. However, the effect was significant only in men [R].

A study of 184 Greek participants confirmed those findings: people with this variant had two times higher odds of being obese. Each copy of the “A” allele was associated with a 3-point increase in body mass index (BMI) [R].

The “AA” genotype correlated with a higher BMI in a study of 452 French subjects. Diabetes patients with this genotype had 4.6 times higher obesity rates [R].

On the other hand, the “GG” genotype was associated with obesity among 300 men from Saudi Arabia, so the effect of this variant might depend on ethnicity [R].

The “A” allele at rs731236 (TaqI) may correlate with obesity among European descendants. The effect is more pronounced in men and diabetes patients.

Fokl (rs2228570)

In the Spanish study mentioned above, the “G” allele at rs2228570 showed a link with higher fat mass, independent of age or sex [R]. A trial of 517 healthy Chinese adults came to a similar conclusion [R].

In both studies, this SNP only correlated with body fat percentage and not weight (BMI).

Rs3782905

Another SNP in the VDR gene might influence body weight: rs3782905 was associated with BMI and waist circumference (WC) among 1,773 US women. Each copy of the less common “C” allele implied a 2.21-cm increase in WC, which is a measure of abdominal obesity [R].

Two more VDR SNPs may correlate with body-weight measures: rs2228570-G with fat mass and rs3782905-C with weight and belly fat.

How It Works

Two SNPs—rs3782905 and rs2228570—may impact VDR gene expression by changing the stability of its transcription products (mRNAs). The obesity-associated alleles likely stimulate gene expression and thus suppress fat-burning UCP proteins [R, R, R].

One paper also confirmed the link between VDR variants and inflammation: people carrying the obesity “risk” alleles had higher levels of IL-1b, IL-6, and TNF-a [R].

Surprisingly, the genetic link between this receptor and fat metabolism may not depend on vitamin D status, but we don’t have a definite answer to that question [R].

The VDR variants may enhance gene expression in the fat tissue. The fat buildup may arise from inflammation and suppressed UCP proteins. 

Limitations

As mentioned, the link between VDR variants and body-weight measures likely depends on different factors such as sex, ethnicity, and health status. 

Some comprehensive trials have failed to replicate the effect of any SNPs in this gene, including the ones discussed above, so you should take the results with a grain of salt [R, R, R].

Although the discussed variants likely enhance VDR expression in fat cells, it may not be a good idea to try and counteract them directly. Increased VDR activity in other tissues has essential benefits for bone health, immunity, and more [R, R, R, R].

SNP Summary

Primary SNP:

VDR rs731236

• ‘A’ = may be associated with obesity in European populations
• ‘G’ = not associated with obesity

Population Frequency: Around 44% of European descendants carry one copy and 38% carry both copies of the “A” allele. It’s even more common in other populations, especially East Asian.

Other Important SNPs:

VDR rs2228570

• ‘A’ = not associated with obesity or fat mass 
• ‘G’ = associated with higher fat mass

Population Frequency: Around 44% of European descendants carry one copy and 40% carry both copies of the “G” allele. It’s even more common in African (96%) and South Asian (93%) populations.

VDR rs3782905

• ‘C’ = may be associated with obesity and higher waist circumference 
• ‘G’ = not associated with obesity

Population Frequency: Around 42% of European descendants carry one copy and 12% carry both copies of the “C” allele. It’s less common in African (38%) and East Asian (28%) populations.