The APOA2 gene provides one of the clearest examples of gene-diet interaction affecting body weight. The rs5082 variant determines how your body responds to saturated fat intake - some people gain weight easily on high saturated fat diets while others are relatively protected. This has practical implications for personalized nutrition.
What is APOA2?
APOA2 (Apolipoprotein A-II) is the second most abundant protein in HDL ("good") cholesterol particles. It plays roles in:
- Lipid metabolism and HDL function
- Regulation of food intake and satiety
- Hepatic fat metabolism
- Insulin sensitivity
The rs5082 variant is in the promoter region of APOA2, affecting gene expression.
Understanding Your Genotype
- TT: Normal response to saturated fat
- TC: Intermediate (but often grouped with CC for risk)
- CC: Increased sensitivity - higher obesity risk with high saturated fat intake
The Gene-Diet Interaction
This is one of the best-replicated nutrigenetic findings:
For CC Genotype
- High saturated fat intake (>22g/day): Significantly higher BMI and obesity risk
- Low saturated fat intake (<22g/day): No elevated risk - similar to other genotypes
- The interaction is specific to saturated fat, not total fat
For TT Genotype
- BMI not strongly affected by saturated fat intake level
- More dietary flexibility regarding saturated fat
- Overall healthy eating still matters for other health outcomes
Practical Dietary Recommendations
For CC Genotype (Saturated Fat Sensitive)
Limit:
- Fatty cuts of red meat
- Full-fat dairy (butter, cream, cheese)
- Coconut oil and palm oil
- Processed foods with high saturated fat
- Baked goods made with butter or shortening
Emphasize:
- Olive oil and avocado oil (monounsaturated fats)
- Fatty fish (omega-3s)
- Nuts and seeds (unsaturated fats)
- Lean protein sources
- Plant-based proteins
For TT Genotype
- More flexibility with saturated fat, but moderation still wise
- Focus on overall diet quality
- Cardiovascular health still benefits from limiting saturated fat regardless of weight effects
Prevalence
- European ancestry: Approximately 10-15% CC
- Other populations: Variable; studies primarily in European populations
Testing with NutraHacker
NutraHacker analyzes APOA2 along with other genes affecting fat metabolism and weight management.
Frequently Asked Questions
Does this mean I should avoid all fat?
No. The interaction is specific to saturated fat. Unsaturated fats (olive oil, fish, nuts) do not show the same interaction with APOA2 and are important for health. Focus on fat quality, not just quantity.
How much saturated fat is too much for CC genotype?
Research suggests the threshold is around 22g/day. For reference, one tablespoon of butter has about 7g saturated fat, and a fast food cheeseburger might have 15-20g. Reading nutrition labels helps track intake.
References
- Corella D, et al. APOA2, dietary fat, and body mass index: replication of a gene-diet interaction in 3 independent populations. Arch Intern Med. 2009;169(20):1897-1906.
- Smith CE, et al. Apolipoprotein A2 polymorphism interacts with intakes of dairy foods to influence body weight in 2 U.S. populations. J Nutr. 2013;143(12):1865-1871.