High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme,
Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of
Nutrient‐Dependent Increases of Blood Pressure
Background Angiotensin‐converting enzyme (ACE) plays a major role in blood
pressure regulation and cardiovascular homeostasis. Contrary to the assumption
that ACE levels are stable, circulating ACE has been shown to be altered in
obesity and weight loss. We sought to examine effects of a high‐saturated‐fat
(HF) diet on ACE within the NUtriGenomic Analysis in Twins (NUGAT) study.
Methods and Results Forty‐six healthy and nonobese twin pairs initially
consumed a carbohydrate‐rich, low‐fat diet over a period of 6 weeks to
standardize for nutritional behavior prior to the study, followed by 6 weeks
of HF diet under isocaloric conditions. After 6 weeks of HF diet, circulating
ACE concentrations increased by 15% (P=1.6×10−30), accompanied by an increased
ACE gene expression in adipose tissue (P=3.8×10−6). Stratification by ACE
rs4343, a proxy for the ACE insertion/deletion polymorphism (I/D), revealed
that homozygous carriers (GG) of the variant had higher baseline ACE
concentrations (P=7.5×10−8) and additionally showed a 2‐fold increase in ACE
concentrations in response to the HF diet as compared to non‐ or heterozygous
carriers (AA/AG, P=2×10−6). GG carriers also responded with higher systolic
blood pressure as compared to AA/AG carriers (P=0.008). The strong gene‐diet
interaction was confirmed in a second independent, cross‐sectional cohort, the
Metabolic Syndrome Berlin Potsdam (MeSyBePo) study. Conclusions The
HF‐diet‐induced increase of ACE serum concentrations reveals ACE to be a
potential molecular link between dietary fat intake and hypertension and
cardiovascular disease (CVD). The GG genotype of the ACE rs4343 polymorphism
represents a robust nutrigenetic marker for an unfavorable response to
high‐saturated‐fat diets. Clinical Trial Registration URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01631123
