Koeijvoets Kristel C M C, van Rossum Elisabeth F C, Dallinga-Thie Geesje M, Steyerberg Ewout W, Defesche Joep C, Kastelein John J P, Lamberts Steven W J, Sijbrands Eric J G
Department of Internal Medicine, D435, Erasmus Medical Center, P.O. Box 2040, 3000 AC Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2006 Oct;91(10):4131-6. doi: 10.1210/jc.2006-0578. Epub 2006 Jul 18.
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.
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.
The primary outcome measure was cardiovascular disease.
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).
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.
