Is This Vitamin D Gene Linked To Lifespan? (VDR)

The VDR gene is responsible for producing a protein called the vitamin D receptor (VDR). This VDR protein goes on to form a complex with vitamin D [R]. 

The VDR and vitamin D complex has many biological effects, some of which include [R]:

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

Because this complex is important for so many systems in the body, genetic variations in the VDR gene have been associated with several disorders, such as infection, cancer, and osteoporosis [R, R, R].

Perhaps, one of the more interesting associations is between VDR and longevity. According to research, certain genetic variations in the VDR gene may be linked to longer lifespans [R, R, R].

How Does VDR Work?

The vitamin D receptor (also known as VDR or the calcitriol receptor) works by binding to the activated form of vitamin D, which is called calcitriol. Once bound together they form a special complex, which has various biological effects.

Some of the functions of the VDR and vitamin D complex include [R, R, R]:

• Promoting the expression of other genes
• Maintaining calcium and phosphorus levels in the blood
• Regulating metabolic pathways involved with immune response and cancer
• Regulating hair loss

Research has identified several genetic variations in the VDR gene which are much more common in those that live exceptionally long lives.

Genetic variations of VDR that may be associated with longevity include [R, R, R]:

• FokI (rs2228570)
• BsmI (rs1544410)
• ApaI (rs7975232)

In the sections below, we’ll go in-depth on each of these variations and the scientific research behind each one.

The FokI Variant

One of the VDR gene variants that may be associated with longevity is in the SNP rs2228570, also known as the FokI polymorphism.

For example, one study of 728 people living in Iran found that the ‘G’ allele was much more common in those that have lived very long lives [R].

On top of that, the same study also suggests that the ‘GG’ genotype is associated with improved cognitive function in the elderly [R].

However, other studies have found conflicting results.

A study of 265 Caucasians from Northern Italy did not find a link between FokI and greater lifespan. Although, researchers did find that the ‘GG’ genotype was associated with better hand grip strength and cognitive function in the elderly [R].

Another study including 309 people of German descent also concluded that the FokI variant is not associated with longevity [R].

The ‘G’ allele in the FokI variant (rs2228570) of VDR was significantly more common in those that lived exceptionally long lives, according to a study looking at participants in Iran. There was no association found with longevity when looking at populations from Italy or Germany.

The BsmI Variant

Another well-researched polymorphism in VDR is the BsmI variant, also known as rs1544410.

According to a study of 265 people from Northern Italy, the ‘CT’ genotype is found much more frequently in those that are 100 years or older [R].

The same study also suggests that the ‘CT’ genotype may be associated with lower systolic blood pressure and better cognitive function in the elderly [R].

The ApaI Variant

A polymorphism in the VDR gene known as ApaI, also known as rs7975232, may also play a role in longevity, according to research.

Based on the previously mentioned study of 265 Northern Italians, the ‘A’ allele of the ApaI variant appears to be more common in people who live past 100 years [R].

The same study also found that the ‘AA’ genotype may be associated with higher blood pressure and lower rates of  chronic obstructive pulmonary disease (COPD) [R].

How Does VDR Improve Longevity?

It’s not entirely clear how these genetic variants in the VDR gene may contribute to longer lifespan. 

The VDR protein and vitamin D have many different functions in the body, so the mechanism behind improved longevity is likely complex and multifaceted [R, R].

One animal study examined the genetic activity of worms in an attempt to identify the potential mechanisms behind the association between vitamin D and longevity. According to the researchers of the study, vitamin D may increase worm lifespan by [R]:

• Activating the SKN-1 gene, which plays a role in stress response and detoxification
• Regulating IRE-1 and XBP-1, which help maintain the balance of healthy proteins

However, this association has not been fully explored in humans.

You can see your genotypes for VDR in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

Primary SNPs: 

VDR rs2228570

• ‘A’ = No association with longevity
• ‘G’ = More common in those with longer lifespans in certain populations
• About 47% of people have the ‘GG’ genotype
• The association with longevity has only been found in people living in Iran
• No association with longevity was found in Italian and German populations

VDR rs1544410

• ‘CC’ & ‘TT’ = No association with longevity 
• ‘CT’ = More common in those with longer lifespans in certain populations
• About 37% of people have the ‘CT’ genotype
• The association with longevity has only been found in groups from Northern Italy

VDR rs7975232

• ‘C’ = No association with longevity 
• ‘A’ = More common in those with longer lifespans in certain populations
• About 29% of people have the ‘AA’ genotype
• The association with longevity has only been found in groups from Northern Italy