Can This Gene Cause Obesity (SEC16B)?

The SEC16B gene encodes a protein also called SEC16B (‘SEC16 homolog B’) [R, R].

SEC16B was first identified as a protein enhancing the expression of the regucalcin gene and called RGPR-p117 (‘regucalcin gene promoter-related protein 117’) [R, R].

SEC16B controls the secretory process by allowing the assembly of the vesicles that transport newly formed proteins and fats out of the membrane system that produces them (the endoplasmic reticulum) [R, R].

Importantly, SEC16B is required for the transport of the factors that promote the formation of peroxisomes. These cell structures are involved in the breakdown of fatty acids [R, R].

The SEC16B gene encodes a protein involved in the secretion of proteins that help transport and break down fat.

Rs10913469 and Rs543874

Two SEC16B polymorphisms have been widely investigated: rs10913469 and rs543874.

The minor ‘C’ variant of rs10913469 was more common among people with obesity and high BMI in Japanese, Chinese, Singaporean, and Dutch adults. However, two studies couldn’t find this association [R, R, R, R, R, R, R, R, R].

This variant has also been linked to increased obesity rates, BMI, and body weight in Czech, Mexican, Portuguese, Chinese, American, Danish, Estonian, Norwegian, and British children and adolescents [R, R, R, R, R, R, R, R, R, R].

The minor ‘G’ variant of rs543874 has been associated with higher obesity rates and BMI in Japanese (especially in women), Korean, and African American populations, and with high body fat percentage in people of European descent [R, R, R, R, R, R]. 

This allele has also been linked to higher rates of childhood obesity, as well as with increases in BMI throughout childhood and adolescence in multiple ethnicities [R, R, R, R, R, R, R, R, R, R].

A meta-analysis of 28 studies concluded that both variants are associated with increased BMI and risk of obesity in different ethnic populations [R].

Other Polymorphisms

Less-widely investigated polymorphisms linked to obesity traits include:

• The minor ‘T’ variant of rs574367: associated with higher BMI in healthy people of East Asian ancestry and Chinese diabetics [R, R]
• The minor ‘A’ variant of rs516636: associated with increased obesity and BMI in Japanese adults and Chinese children [R, R]
• The minor ‘C’ variant of rs591120: associated with increased BMI in European adolescents and young adults [R, R]

How It Works

Unfortunately, none of the studies evaluated the effects of the different variants on SEC16B expression. 

The exact contribution of this protein to weight also remains unclear, but the following mechanisms have been proposed:

• As previously mentioned, SEC16B stimulates the production of the regulatory protein regucalcin. Its excessive levels increase fat production in bone marrow cells and alter fat transport in rats, leading to increased fat levels in blood but lower in the liver [R, R, R].
• Mutated SEC16B variants may reduce fat breakdown by interfering with the correct formation of peroxisomes [R, R].
• SEC16B may contribute to weight gain through its role in protein secretion. Variants of this gene could alter the transport of proteins involved in appetite regulation or fat breakdown [R, R].
• SEC16B might influence the diet by changing taste preferences [R, R].

The minor variants of several SEC16B polymorphisms have been associated with increased obesity rates and BMI. The mechanisms by which they contribute to weight gain remain unclear.

SNP Summary and Table

Primary SNP:

SEC16B rs10913469 

• ‘T’ = normal obesity rates, BMI, and body weight
• ‘C’ = increased obesity rates, BMI, and body weight
• 60% of the world population carries two copies of the ‘T’ allele
• The ‘C’ variant is slightly more common in people with an African background

Other Important SNPs:

SEC16B rs543874 

• ‘A’ =  normal obesity rates, BMI, and body fat
• ‘G’ = increased obesity rates, BMI, and body fat
• Less than 5% of the world population carries two copies of the ‘G’ allele
• The ‘A’ variant is even more common in people of East and South Asian ancestry and less in African descendants

SEC16B rs574367

• ‘G’ = normal BMI
• ‘T’ = increased BMI
• Less than 3% of the world population carries two copies of the ‘T’ allele
• The ‘T’ variant is even less common in African descendants

SEC16B rs516636

• ‘C’ = normal obesity rates and BMI
• ‘A’ = increased obesity rates and BMI
• The genotype distribution is very similar to that of rs574367 for all ethnicities
• The ‘A’ variant is slightly more common in people of European and American descent

SEC16B rs591120

• ‘G’ = normal BMI 
• ‘C’ = increased BMI
• Approximately 47% of the world population carries one copy of each allele
• The ‘C’ variant is least common in East Asian descendants