BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function: The Hoorn and CODAM Studies

Dirk van Moorsel; Ronald M. Henry; Nicolaas C. Schaper; Marleen M. van Greevenbroek; Elisabeth F. van Rossum; Leen M. 't Hart; Casper G. Schalkwijk; Carla J. van der Kallen; Jacqueline M. Dekker; Coen D. Stehouwer; Bas Havekes

doi:10.1093/ajh/hpw196

BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function: The Hoorn and CODAM Studies

Dirk van Moorsel, Ronald M. Henry, Nicolaas C. Schaper, Marleen M. van Greevenbroek, Elisabeth F. van Rossum, Leen M. 't Hart, Casper G. Schalkwijk, Carla J. van der Kallen, Jacqueline M. Dekker, Coen D. Stehouwer, Bas Havekes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND

Chronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function.

METHODS

We conducted an observational cohort study, combining 2 cohort studies designed to investigate genetic and metabolic determinants of CVD. We genotyped 1,124 individuals (age: 64.7 +/- 8.5 years) from the Hoorn study and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study for BclI. Several arterial stiffening indices of the carotid (Hoorn and CODAM study), brachial and femoral artery and the carotid-femoral pulse wave velocity (Hoorn study only) were determined. In addition, in the Hoorn study, we determined several variables of cardiac structure and function.

RESULTS

We identified 155 homozygous carriers (GG), 498 heterozygous carriers (CG), and 471 noncarriers (CC) of the BclI polymorphism. BclI genotypes did not display significant differences in variables of arterial stiffening (e.g., carotid distensibility coefficient (DC): 12.41 +/- 5.37 vs. 12.87 +/- 5.55 10(-3)/kPa [mean +/- SD]; P = 0.38; homozygous vs. noncarriers). In addition, no clear differences in estimates of cardiac structure and function were found.

CONCLUSIONS

Even though BclI is associated with a higher BMI and some proxies of CVD, our results do not support the concept that BclI carrier status is associated with greater arterial stiffening or cardiac dysfunction.

Original language	English
Pages (from-to)	286-294
Number of pages	9
Journal	American Journal of Hypertension
Volume	30
Issue number	3
DOIs	https://doi.org/10.1093/ajh/hpw196
Publication status	Published - Mar 2017

Keywords

arterial stiffness
arterial stiffening
BclI
blood pressure
cardiac function
cardiac structure
glucocorticoids
glucocorticoid receptor
glucocorticoid receptor polymorphism
hypertension
left ventricular function
rs41423247
DETERIORATING GLUCOSE-TOLERANCE
DIASTOLIC DYSFUNCTION
EJECTION FRACTION
CUSHINGS-SYNDROME
AORTIC STIFFNESS
ALL-CAUSE
IN-VIVO
METABOLISM
DISEASE
GENE

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van Moorsel, D., Henry, R. M., Schaper, N. C., van Greevenbroek, M. M., van Rossum, E. F., 't Hart, L. M., Schalkwijk, C. G., van der Kallen, C. J., Dekker, J. M., Stehouwer, C. D., & Havekes, B. (2017). BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function: The Hoorn and CODAM Studies. American Journal of Hypertension, 30(3), 286-294. https://doi.org/10.1093/ajh/hpw196

@article{91a9afed36ed448493f6f300f77dfd4b,

title = "BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function: The Hoorn and CODAM Studies",

abstract = "BACKGROUNDChronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function.METHODSWe conducted an observational cohort study, combining 2 cohort studies designed to investigate genetic and metabolic determinants of CVD. We genotyped 1,124 individuals (age: 64.7 +/- 8.5 years) from the Hoorn study and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study for BclI. Several arterial stiffening indices of the carotid (Hoorn and CODAM study), brachial and femoral artery and the carotid-femoral pulse wave velocity (Hoorn study only) were determined. In addition, in the Hoorn study, we determined several variables of cardiac structure and function.RESULTSWe identified 155 homozygous carriers (GG), 498 heterozygous carriers (CG), and 471 noncarriers (CC) of the BclI polymorphism. BclI genotypes did not display significant differences in variables of arterial stiffening (e.g., carotid distensibility coefficient (DC): 12.41 +/- 5.37 vs. 12.87 +/- 5.55 10(-3)/kPa [mean +/- SD]; P = 0.38; homozygous vs. noncarriers). In addition, no clear differences in estimates of cardiac structure and function were found.CONCLUSIONSEven though BclI is associated with a higher BMI and some proxies of CVD, our results do not support the concept that BclI carrier status is associated with greater arterial stiffening or cardiac dysfunction.",

keywords = "arterial stiffness, arterial stiffening, BclI, blood pressure, cardiac function, cardiac structure, glucocorticoids, glucocorticoid receptor, glucocorticoid receptor polymorphism, hypertension, left ventricular function, rs41423247, DETERIORATING GLUCOSE-TOLERANCE, DIASTOLIC DYSFUNCTION, EJECTION FRACTION, CUSHINGS-SYNDROME, AORTIC STIFFNESS, ALL-CAUSE, IN-VIVO, METABOLISM, DISEASE, GENE",

author = "{van Moorsel}, Dirk and Henry, {Ronald M.} and Schaper, {Nicolaas C.} and {van Greevenbroek}, {Marleen M.} and {van Rossum}, {Elisabeth F.} and {'t Hart}, {Leen M.} and Schalkwijk, {Casper G.} and {van der Kallen}, {Carla J.} and Dekker, {Jacqueline M.} and Stehouwer, {Coen D.} and Bas Havekes",

year = "2017",

month = mar,

doi = "10.1093/ajh/hpw196",

language = "English",

volume = "30",

pages = "286--294",

journal = "American Journal of Hypertension",

issn = "0895-7061",

publisher = "Oxford University Press",

number = "3",

}

van Moorsel, D, Henry, RM, Schaper, NC, van Greevenbroek, MM, van Rossum, EF, 't Hart, LM, Schalkwijk, CG , van der Kallen, CJ, Dekker, JM, Stehouwer, CD & Havekes, B 2017, 'BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function: The Hoorn and CODAM Studies', American Journal of Hypertension, vol. 30, no. 3, pp. 286-294. https://doi.org/10.1093/ajh/hpw196

TY - JOUR

T1 - BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function

T2 - The Hoorn and CODAM Studies

AU - van Moorsel, Dirk

AU - Henry, Ronald M.

AU - Schaper, Nicolaas C.

AU - van Greevenbroek, Marleen M.

AU - van Rossum, Elisabeth F.

AU - 't Hart, Leen M.

AU - Schalkwijk, Casper G.

AU - van der Kallen, Carla J.

AU - Dekker, Jacqueline M.

AU - Stehouwer, Coen D.

AU - Havekes, Bas

PY - 2017/3

Y1 - 2017/3

N2 - BACKGROUNDChronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function.METHODSWe conducted an observational cohort study, combining 2 cohort studies designed to investigate genetic and metabolic determinants of CVD. We genotyped 1,124 individuals (age: 64.7 +/- 8.5 years) from the Hoorn study and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study for BclI. Several arterial stiffening indices of the carotid (Hoorn and CODAM study), brachial and femoral artery and the carotid-femoral pulse wave velocity (Hoorn study only) were determined. In addition, in the Hoorn study, we determined several variables of cardiac structure and function.RESULTSWe identified 155 homozygous carriers (GG), 498 heterozygous carriers (CG), and 471 noncarriers (CC) of the BclI polymorphism. BclI genotypes did not display significant differences in variables of arterial stiffening (e.g., carotid distensibility coefficient (DC): 12.41 +/- 5.37 vs. 12.87 +/- 5.55 10(-3)/kPa [mean +/- SD]; P = 0.38; homozygous vs. noncarriers). In addition, no clear differences in estimates of cardiac structure and function were found.CONCLUSIONSEven though BclI is associated with a higher BMI and some proxies of CVD, our results do not support the concept that BclI carrier status is associated with greater arterial stiffening or cardiac dysfunction.

AB - BACKGROUNDChronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function.METHODSWe conducted an observational cohort study, combining 2 cohort studies designed to investigate genetic and metabolic determinants of CVD. We genotyped 1,124 individuals (age: 64.7 +/- 8.5 years) from the Hoorn study and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study for BclI. Several arterial stiffening indices of the carotid (Hoorn and CODAM study), brachial and femoral artery and the carotid-femoral pulse wave velocity (Hoorn study only) were determined. In addition, in the Hoorn study, we determined several variables of cardiac structure and function.RESULTSWe identified 155 homozygous carriers (GG), 498 heterozygous carriers (CG), and 471 noncarriers (CC) of the BclI polymorphism. BclI genotypes did not display significant differences in variables of arterial stiffening (e.g., carotid distensibility coefficient (DC): 12.41 +/- 5.37 vs. 12.87 +/- 5.55 10(-3)/kPa [mean +/- SD]; P = 0.38; homozygous vs. noncarriers). In addition, no clear differences in estimates of cardiac structure and function were found.CONCLUSIONSEven though BclI is associated with a higher BMI and some proxies of CVD, our results do not support the concept that BclI carrier status is associated with greater arterial stiffening or cardiac dysfunction.

KW - arterial stiffness

KW - arterial stiffening

KW - BclI

KW - blood pressure

KW - cardiac function

KW - cardiac structure

KW - glucocorticoids

KW - glucocorticoid receptor

KW - glucocorticoid receptor polymorphism

KW - hypertension

KW - left ventricular function

KW - rs41423247

KW - DETERIORATING GLUCOSE-TOLERANCE

KW - DIASTOLIC DYSFUNCTION

KW - EJECTION FRACTION

KW - CUSHINGS-SYNDROME

KW - AORTIC STIFFNESS

KW - ALL-CAUSE

KW - IN-VIVO

KW - METABOLISM

KW - DISEASE

KW - GENE

U2 - 10.1093/ajh/hpw196

DO - 10.1093/ajh/hpw196

M3 - Article

SN - 0895-7061

VL - 30

SP - 286

EP - 294

JO - American Journal of Hypertension

JF - American Journal of Hypertension

IS - 3

ER -