Population Distribution of CES1 Genetic Variants
Susan E. King, Hannah Coziahr, Ming Wang, Jacob Wang, Judy Q. WuBackground:
Treatment-resistant hypertension is a widespread issue affecting individuals throughout the world. CES1 is a phase-1 drug-metabolizing enzyme responsible for hydrolyzing multiple medications, with Angiotensin-Converting Enzyme (ACE) inhibitors being one drug class affected. Genetic variations in the structure of CES1 can significantly diminish its ability to metabolize ACE inhibitors into active compounds to treat hypertension. The objective of this study is to describe the prevalence of 24 variants of CES1 in the All of Us Controlled Tier Dataset v8 population.
Methods:
The study included all adult participants in the All of Us Controlled Tier Dataset v8 as of March, 2025. We created cohorts within the All of Us researcher workbench for each CES1 gene SNP, with inclusion criteria consisting of each individual gene as well as all races, ethnicities, genders, and sex at birth. Jupyter was used for the analysis of the demographics of each cohort in the Python programming language. Statistical analyses were performed using R (version 4.5.1).
Results:
A total of 1,700,515 variants were identified, of which 311,182 had decreased function, and 1,393,632 retained normal function. There were an average of 3.45 variants per person, with the range unknown. There were statistically significant differences in the ethnic distribution of decreased-function variants.
Discussion:
Patients of all racial and ethnic demographics experience treatment-resistant hypertension. Genetic variations in CES1 could be a contributing factor, as these are present in all racial/ethnic groups to varying degrees. In particular, the 95% loss-of-function alleles occur primarily in specific racial/ethnic populations.
Conclusions:
Genetic variations in CES1 exhibit non-uniform population distribution. These structural variations can lead to inadequate clinical management of hypertension.