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By Kristin Bundy

Reviewed by Nihar Desai, MD, MPH, Assistant Professor of Medicine (Cardiology), Yale School of Medicine, New Haven, Connecticut

Take Note

  • Angiotensin converting enzyme (ACE) plays a role in cardiovascular homeostasis and blood pressure regulation.
  • A high-fat diet, independent of weight gain was shown to increase serum ACE concentrations.
  • Homozygous carriers of the ACE rs4343 variant had higher levels of ACE concentrations at baseline than heterozygous carriers or homozygous noncarriers; after 6-weeks of a diet high in saturated fats, they also had higher blood pressure.


Cardiovascular homeostasis and blood pressure are regulated in part by angiotensin converting enzyme (ACE).1 Serum concentrations of ACE were once thought to remain relatively stable, but recent research has shown that ACE levels increase with weight gain and decrease with weight loss.1 In a study published in the Journal of the American Heart Association,1 investigators examined whether serum ACE concentrations fluctuate with one’s diet, independent of weight gain, and if genetic factors are involved.

Forty-six pairs of twins who were relatively young (mean age 31) and nonobese (mean BMI 23 kg/m2) were included in the study.1 Subjects were first directed to eat a low-fat diet for 6 weeks (LF: 55% carbohydrates, 30% fats, and 15% protein). During the following 6 weeks, they were directed to eat a diet high in saturated fats (HF: 40% carbohydrates, 45% fat, and 15% protein). The total calories consumed during each 6-week period were similar.

After 6 weeks of a high-fat diet, fasting serum ACE concentrations rose by 15%—a significant increase independent of weight gain.1 The researchers also found that ACE gene expression in adipose tissue significantly increased. Using a proxy for ACE insertion/deletion polymorphism, ACE rs4343, the study was stratified by carriers of the variant: homozygous (GG), heterozygous (AG), and homozygous noncarriers (AA). Those with GG had higher ACE concentrations at baseline, and after the high-fat diet, had higher systolic blood pressure and twice the increase in ACE concentration as compared with patients with AG and AA genotypes.

Lead author Rita Schüler, PhD, from the Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam?Rehbrücke (DIfE), Nuthetal, Germany, noted that “the identification of such a strong gene-diet interaction on blood pressure in rather young and healthy study participants” was the most surprising finding—one which could change the course of screening and treatment of CVD.

Dr. Schüler explained, “Determination of individuals‘ rs4343 genotype could be utilized for patients with hypertension or borderline hypertension. Carriers of the ACE rs4343 variant (GG-genotype) would be expected to benefit from avoiding diets high in total and saturated fat. Furthermore, it is conceivable that patients with borderline hypertension carrying the GG-genotype would profit from adherence to a diet with low to moderate fat content in the manner that they might no longer need any medication.”

Nutrigenetic markers, like ACE rs4343 genotypes, are not commonly used in clinical practice because it’s a relatively new field of study, noted Dr. Schüler. But that may soon change. The study authors said in a press release that, if their results are confirmed in larger studies, it’s possible that ACE rs4343 could be used as a biomarker for cardiovascular disease risk, similar to how LDL cholesterol is used now.2

So what can clinicians glean from what was published in this study? Dr. Schüler concluded, “Our results are important with respect to the elimination of the upper limits on dietary fat intake in the US dietary guidelines and show that a diet high in total and saturated fat is detrimental, at least for certain individuals, based on their genetic setting. Furthermore, our findings support the need for providing personalized dietary recommendations to assist in disease management and prevention.”

Published: 03/10/2017


Deutsches Zentrum fur Diabetesforschung (DZD). Gene variant in conjunction with high-fat diet linked to increased blood pressure.