Are You Genetically Suited for a High-Protein Diet? (TFAP2B)

The TFAP2B gene codes for a protein called transcription factor AP-2B, which can attach to DNA and control the activity of other genes. TFAP2B has the power to influence how cells divide and self-destruct when they are no longer needed (also known as apoptosis) [R].

Although we aren’t aware of it, this unusual protein starts to play a large part in our lives even before we are born. Research shows that TFAP2B is active in cells in the early prenatal period, affecting how the brain and other tissues and organs develop [R].

More recently, the TFAP2B gene has been in the spotlight of obesity and nutrigenomics research. So what do your TFAP2B variants mean and how exactly can you modify your diet based on them?

The TFAP2B gene is implicated in prenatal development, obesity, and dietary response. 

TFAP2B, BMI & Being Overweight

Variations in the TFAP2B gene have been associated with increased weight and belly fat and type 2 diabetes. The majority of obesity and diet-related research focused on a SNP labeled rs987237 [R, R]. 

Initial studies revealed a link between the G allele of rs987237 and obesity. People carrying the risk allele were more likely to be overweight and to have excess belly fat [R]. 

The TFAP2B gene is mostly expressed in fat tissue and it is more active in people with the risk allele. Scientists think that TFAP2B overactivity might cause the body to store too much fat by inducing insulin resistance in fat cells. It also reduces adiponectin and increases interleukin-6 (IL-6) [R, R, R]. 

Low adiponectin levels have been linked with obesity, insulin resistance, and heart disease. IL-6 is an inflammatory cytokine. Hence, TFAP2B seems a plausible link between obesity and low-grade inflammation [R, R]. 

This gene also appears to increase the size of fat cells. Switching TFAP2B on in test tubes transformed regular cells into massive, dangerous fat cells that are characteristic of obesity [R]. 

Although more research is needed, it seems that keeping TFAP2B from becoming overactive might be beneficial for weight loss and general well-being [R]. 

Certain genetic variations may over-activate the TFAP2B gene, potentially contributing to obesity and insulin resistance. 

The existing studies suggest that people who carry TFAP2B risk variants tend to have extra weight, and they may be better off on a high-fat diet [R]. 

High-protein diets are well researched for curbing appetite and preventing weight regain. However, people with TFAP2B variations seem to be an exception: they might be more prone to the “yo-yo” effect with high protein intake [R]. 

This association is still inconclusive, though, since only a couple of studies on TFAP2B and diet have been published so far. 

Remember that many other genetic and non-genetic factors also influence a person’s response to diet and their ability to lose weight. Dietary interventions should always be part of a holistic weight management program that takes these factors and your overall health into account. 

Weight Loss Based on Fat Intake

A study of obese adults revealed an association between the more common TFAP2B rs987237 genotype and weight loss on a low-fat diet. The rare genotype was linked with weight loss on a high-fat diet [R]. 

Both diets were energy-deficient (by 600 kcal) and the participants strictly followed them for 10 weeks. 

To take a deep dive into the data by genotype:

• AA carriers lost over 2lbs (1 kg) more weight on the low-fat than on the high-fat diet
• GG carriers (highest obesity risk) lost almost 6 lbs (2.6 kg) more weight on the high-fat diet 
• GA carriers were a bit less sensitive, but they still lost almost 2 lbs (0.8 kg) more on the high-fat diet

The authors also discovered a similar but weaker pattern for waist size reduction. People with the AA genotype lost more belly fat on the low-fat diet, and vice versa [R]. 

Another study of 639 obese people found a similar but insignificant trend. Participants in this study dieted for only 8 weeks and were not closely monitored, which might explain the weaker effect [R]. 

People with obesity-linked TFAP2B rs987237 variations (GG and AG) are likely to lose more weight on high-fat diets. The opposite seems to be the case for obese AA carriers.

Will You Regain Weight on Protein or Fat?

Preventing weight regain–the infamous “yo-yo” effect–might be even more important than losing extra weight in the first place. Maintaining healthy weight and good nutrition is key to fighting obesity and other chronic health problems in the long run [R]. 

People often describe this maintenance step as more challenging than initial weight loss. It’s not just about “sticking to it” and having psychological support. The body actually mounts a response when you lose weight, activating various feedback loops you have to overcome. In turn, your hormones change, your appetite increases, and you feel less satiated [R]. 

And as it turns out, people may have completely opposite weight regain reactions to high fat vs. high-protein diets based on TFAP2B variations [R]. 

In a study of 468 people, high-protein diets were beneficial for weight maintenance in the “non-risk” AA  rs987237 genotype group. 

Carriers of the obesity risk allele (G allele) regained 4 lbs more body weight per risk allele on the high-protein diet compared to the low-protein diet. In other words, people with the GG genotype regained 8 lbs more when their protein intake was high.

High-protein diets may be a good weight-maintenance strategy for most people. People with obesity-linked rs987237 variations may be better suited for lower protein intake. 

SNP Summary and Table

You can see your genotypes for TFAP2B 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 SNP: TFAP2B rs987237 

• ‘A’ = Greater weight loss on lower-fat diets, better weight maintenance on a high-protein diet; less prone to obesity. 
• ‘G’ = Greater weight loss on higher-fat diets, better weight maintenance on a low-protein diet; more likely to be obese. 

Population Frequency

Around 68% of people worldwide carry the high-protein-suited, “non-obesity” AA variant of rs987237; the rest are mostly AG (28%), while about 4% carry two risk alleles (GG). 

The situation flips in Latin Americans, of which only 45% are AA. Let’s take a closer look:

• Only 31% of people of Mexican ancestry are AA. The rest carry the fat-favoring, “obesity” risk allele (48% are AG and a shocking 20% have the highest risk GG genotype)
• Similarly, only 30% of Peruvians are AA (52% are AG and 18% are GG)

On the other end of the spectrum are people of African ancestry, 84% of which have the “non-obesity” AA variant. About 16% are AG; the highest risk, GG allele is extremely rare (under 1%).

The rest are somewhere in-between: 67% of Europeans are AA, while 73% of East Asians and 59% of South Asians are AA. 

Although the “obesity” G allele of rs987237 is considered the rare variant worldwide, it’s relatively more common among people of South and Central American ancestry.