TY - JOUR
T1 - A functional polymorphism in the glucocorticoid receptor gene and its relation to cardiovascular disease risk in familial hypercholesterolemia
AU - Koeijvoets, Kristel C. M. C.
AU - van Rossum, Elisabeth F. C.
AU - Dallinga-Thie, Geesje M.
AU - Steyerberg, Ewout W.
AU - Defesche, Joep C.
AU - Kastelein, John J. P.
AU - Lamberts, Steven W. J.
AU - Sijbrands, Eric J. G.
PY - 2006
Y1 - 2006
N2 - 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
AB - 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
U2 - https://doi.org/10.1210/jc.2006-0578
DO - https://doi.org/10.1210/jc.2006-0578
M3 - Article
C2 - 16849409
SN - 0021-972X
VL - 91
SP - 4131
EP - 4136
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 10
ER -