Saturated Fat and Your Genes (ACE gene)

There has been a decades-long debate about which type of fat is best: saturated fat vs polyunsaturated fat.

Those in the paleo and ketogenic world are quick to tout the benefits of saturated fat, while others, such as the American Heart Association, promote polyunsaturated fats[ref]. And most people remain just a bit confused about the arguments on either side…

Is Saturated Fat Good for You?

It may depend on your genes as to which answer is right for you.

There have been several studies that investigated the effects of a high saturated fat diet on cardiovascular disease – stratified by genetic variants.

Keep in mind that most of these studies are looking at higher saturated fat consumption along with a standard diet (some carbs, some protein, higher fat). The study results may or may not hold true for people on a ketogenic diet.

Let’s take a look at the science so that you can figure out what is right for your genes.

Saturated Fats Genotype Report

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ACE (angiotensin-converting enzyme) gene:

The angiotensin-converting enzyme (ACE) plays a role in maintaining blood pressure at a normal level. It works within the body’s blood pressure regulation system, converting angiotensin I into angiotensin II.  Like most of our body’s systems, the right amount of angiotensin II is key: too much will cause blood vessels to constrict and a subsequent increase in blood pressure.

There is a fairly common genetic variant in the ACE gene that impacts levels of angiotensin-converting enzyme. About 20% of people have the ACE deletion/deletion genotype.

Researchers looked at the interaction between ACE deletion and saturated fat intake. People with the ACE deletion/deletion genotype had an increase in blood pressure on a diet higher in saturated fat. There was also an increase in heart disease. In people without the ACE deletion/deletion variant, saturated fat consumption had no effect on the risk of heart disease.[ref]

Another study found that a high-fat diet caused impaired glucose tolerance in people with ACE deletion. The study looked at the effects of a longer-term (6 weeks in the study) high-fat diet. For people with the ACE deletion/deletion genotype, 6-weeks on the high-fat diet doubled their risk for diabetes.[ref]

Check your genetic data for rs4343 (23andMe v4, v5; AncestryDNA):

  • A/A: typical response to saturated fat (ACE insertion/insertion)
  • A/G: typical response to saturated fat (heterozygous – ACE deletion/insertion)
  • G/G: ACE deletion/deletion  — a high saturated fat diet may increase blood pressure and risk of heart disease[ref], a long-term high-fat diet may also impair glucose tolerance[ref]

Members: Your genotype for rs4343 is .

APOA2 gene:

The protein produced by APOA2 is a type of high-density lipoprotein (HDL).

Genetic variants can result in either APOA2 deficiency or hypercholesteremia (high cholesterol).

The most commonly studied variant, rs5082, decreases the level of APOA2. It has been linked to increased BMI, visceral fat, HDL levels, and a lower risk of heart disease. The studies that looked at the interaction of this variant with different diets found an increased risk for obesity only in those who had a higher saturated fat intake ( >22g of saturated fat). The variant is also linked to ghrelin (hunger hormone) levels, so it is thought that impaired satiety signaling from the saturated fat may play a role in the higher intake of food for those with the variant.[ref][ref]

A study in the journal Nutrition took the link between saturated fat, APOA2 variant, and obesity one step further and looked into the role of saturated fat from dairy.  The conclusion was that higher-fat dairy increases the risk of obesity with the rs5082 G/G genotype.[ref]

Check your genetic data for rs5082 (23andMe v4; v5; AncestryDNA):

  • A/A: typical
  • A/G:  typical risk of obesity with high fat intake
  • G/G: increased risk of obesity, especially with high saturated fat consumption[ref][ref]

Members: Your genotype for rs5082 is .

TCF7L2 Gene:

TCF7L2 is a transcription factor gene that has been linked in numerous studies to an increased risk of type 2 diabetes.

  • The variant causes a significant increase in triglycerides and total cholesterol when consuming a high saturated fat meal.[ref]
  • Another study linked the variant to an increased risk of metabolic syndrome in women, with an even greater risk for those eating a diet higher in saturated fat.[ref]
  • Both metabolic syndrome and high triglycerides are linked to an increased risk of heart disease in many studies.

Check your genetic data for rs7903146 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: typical risk with high fat, generally higher risk of type 2 diabetes
  • T/T: increased risk of metabolic syndrome, especially with high saturated fat consumption; increased risk of T2D

Members: Your genotype for rs7903146 is .

APOE gene:

The APOE E4 allele increases the risk of Alzheimer’s disease. APOE is an apolipoprotein involved in cholesterol transport.

In addition to the well-known link to Alzheimer’s, the APOE E4 allele is also linked to an increased risk of heart disease. A meta-analysis of a bunch of studies shows a 42% increase in heart disease risk for E4 allele carriers.[ref] People with the APOE E4 allele tend to have higher LDL-c, total cholesterol, and HDL levels.[ref]

But the differences in cholesterol levels and other heart-related indices can vary a lot – based on saturated fat consumption.

A 2018 study found that replacing saturated fat with low-glycemic index carbohydrates was most effective at decreasing LDL cholesterol and triglyceride levels in people who carried the E4 allele.[ref]

To determine your APOE type from your 23andMe data, you will need to look at two different alleles (in the table below).

Note: AncestryDNA data is often invalid for determining the APOE genotype.

APOE Allele rs429358 rs7412
ε2/ε2 T/T T/T
ε2/ε3 T/T C/T
ε2/ε4 C/T C/T
ε3/ε3 T/T C/C
ε3/ε4 C/T C/C increased risk of heart disease with a high saturated fat diet
ε4/ε4 C/C C/C increased risk of heart disease with a high saturated fat diet



We are all different in our dietary needs. If you have the variants listed above, you may want to decrease the amount of saturated fat in your diet.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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