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Updated: Aug 7, 2026

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
A functional polymorphism in the glucocorticoid receptor gene and its relation to cardiovascular disease risk in
Kristel C M C Koeijvoets1, Elisabeth F C van Rossum, Geesje M Dallinga-Thie
1Department of Internal Medicine, D435, Erasmus Medical Center, P.O. Box 2040, 3000 AC Rotterdam, The Netherlands.
Context:
Individuals with the functional ER22/23EK variant in the glucocorticoid receptor gene are relatively resistant to the downstream consequences of glucocorticoids. Evidence suggests that carriers have a more favorable cardiovascular risk profile, but the relationship between this ER22/23EK variant and cardiovascular disease has not been hitherto assessed.
Objective:
We, therefore, determined whether carriership of the ER22/23EK improves cardiovascular disease risk in patients with severe hypercholesterolemia.
Design, Setting, And Participants:
In a multicenter cohort study, 2024 patients with heterozygous familial hypercholesterolemia, aged 18 yr and older, were genotyped for the ER22/23EK polymorphism. Patients were identified at lipid clinics throughout The Netherlands between 1989 and 2002.
Main Outcome Measures:
The primary outcome measure was cardiovascular disease.
Results:
Seventy-six (7.8%) of 977 men and 72 (6.9%) of 1047 women were carriers of the ER22/23EK variant. A total of 395 men and 247 women had a cardiovascular event. In contrast to expected results, we observed no significant association of the ER22/23EK variant with cardiovascular disease risk (men: relative risk, 0.75; 95% confidence interval, 0.50-1.14; P = 0.2; women: relative risk, 1.37; 95% confidence interval, 0.82-2.28; P = 0.2). However, we found a significant interaction between gender and the polymorphism on cardiovascular disease (P = 0.02).
Conclusions:
In this large cohort of individuals with very high risk of cardiovascular disease, the association between the functional ER22/23EK polymorphism and cardiovascular risk was not significant overall, although it varied significantly by gender.
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