Glucocorticoid receptor-9beta polymorphism is associated with systolic blood pressure and heart growth during early childhood. The Generation R Study

被引:20
作者
Geelhoed, J. J. Miranda [1 ,2 ,3 ]
van Duijn, Cornelia [2 ]
van Osch-Gevers, Lennie [3 ]
Steegers, Eric A. P. [4 ]
Hofman, Albert [2 ]
Helbing, Willem A. [3 ]
Jaddoe, Vincent W. V. [1 ,2 ,3 ]
机构
[1] Erasmus MC, Generat R Study Grp, NL-3000 CA Rotterdam, Netherlands
[2] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands
[3] Erasmus MC, Dept Pediat, NL-3000 CA Rotterdam, Netherlands
[4] Erasmus MC, Dept Obstet & Gynecol, NL-3000 CA Rotterdam, Netherlands
关键词
Left cardiac structures; Glucocorticoid receptor gene (NR3C1); rs6198; Epidemiology; Cardiovascular disease; LEFT-VENTRICULAR HYPERTROPHY; PROMOTER POLYMORPHISM; BETA-ISOFORM; GENE VARIANT; DEXAMETHASONE; MULTICENTER; SENSITIVITY; EXPRESSION; STABILITY; HAPLOTYPE;
D O I
10.1016/j.earlhumdev.2010.11.006
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Background: Glucocorticoid receptor-9 beta polymorphism (rs6198) is associated with the susceptibility for cardiovascular disease. Aim: To examine whether the GR-9 beta variant is also associated with blood pressure and heart growth in early childhood. Study design: This study was embedded in a population-based prospective cohort study from fetal life onwards. Analyses were based on 857 children. Outcome measures: Left cardiac structures (aortic root diameter, left atrial diameter and left ventricular mass), shortening fraction and heart beat were measured postnatally at the ages of 1.5, 6 and 24 months. Blood pressure was measured at 24 months of age. Results: The distribution of the GR-9 beta genotype showed 75.1% homozygous reference, 23.5% heterozygous and 1.4% homozygous variant subjects. No differences in cardiovascular outcomes were observed at the ages of 1.5 and 6 months. At the age of 24 months, homozygous variants showed an increased systolic blood pressure of 2.65 mm Hg (95% Cl: 0.16, 5.14), an increased heart rate of 9.10 beats per minute (95% Cl: 1.28, 16.7) and an increased left ventricular mass of 4.99g (95% Cl: 1.33, 8.65) compared to homozygous references. This means an increase of 2.6%, 8.6% and 16%, respectively. GR-9 beta polymorphism was significantly associated with left ventricular mass growth during the first 2 years. Conclusion: Our findings suggest that genetically determined differences in cortisol exposure affect cardiovascular development in early life. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:97 / 102
页数:6
相关论文
共 28 条
[1]   Long-term cardiovascular effects of neonatal dexamethasone treatment: hemodynamic follow-up by left ventricular pressure-volume loops in rats [J].
Bal, Miriam P. ;
de Vries, Willem B. ;
van Oosterhout, Matthijs F. M. ;
Baan, Jan ;
van der Wall, Ernst E. ;
van Bel, Frank ;
Steendijk, Paul .
JOURNAL OF APPLIED PHYSIOLOGY, 2008, 104 (02) :446-450
[2]   GLUCOCORTICOID RECEPTOR-BETA, A POTENTIAL ENDOGENOUS INHIBITOR OF GLUCOCORTICOID ACTION IN HUMANS [J].
BAMBERGER, CM ;
BAMBERGER, AM ;
DECASTRO, M ;
CHROUSOS, GP .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2435-2441
[3]   DNA REGULATORY ELEMENTS FOR STEROID-HORMONES [J].
BEATO, M ;
CHALEPAKIS, G ;
SCHAUER, M ;
SLATER, EP .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1989, 32 (05) :737-748
[4]  
BRUCE S, 2002, AAMI
[5]   Glucocorticoid Receptor Gene Variant in the 3′ Untranslated Region Is Associated with Multiple Measures of Blood Pressure [J].
Chung, Charles C. ;
Shimmin, Lawrence ;
Natarajan, Sivamani ;
Hanis, Craig L. ;
Boerwinkle, Eric ;
Hixson, James E. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (01) :268-276
[6]  
Derijk RH, 2001, J RHEUMATOL, V28, P2383
[7]   ECHOCARDIOGRAPHIC ASSESSMENT OF LEFT-VENTRICULAR HYPERTROPHY - COMPARISON TO NECROPSY FINDINGS [J].
DEVEREUX, RB ;
ALONSO, DR ;
LUTAS, EM ;
GOTTLIEB, GJ ;
CAMPO, E ;
SACHS, I ;
REICHEK, N .
AMERICAN JOURNAL OF CARDIOLOGY, 1986, 57 (06) :450-458
[8]   Endocrine and metabolic programming during intrauterine development [J].
Fowden, AL ;
Giussani, DA ;
Forhead, AJ .
EARLY HUMAN DEVELOPMENT, 2005, 81 (09) :723-734
[9]   Cortisol stimulates cell cycle activity in the cardiomyocyte of the sheep fetus [J].
Giraud, G. D. ;
Louey, S. ;
Jonker, S. ;
Schultz, J. ;
Thornburg, K. L. .
ENDOCRINOLOGY, 2006, 147 (08) :3643-3649
[10]   PRIMARY STRUCTURE AND EXPRESSION OF A FUNCTIONAL HUMAN GLUCOCORTICOID RECEPTOR CDNA [J].
HOLLENBERG, SM ;
WEINBERGER, C ;
ONG, ES ;
CERELLI, G ;
ORO, A ;
LEBO, R ;
THOMPSON, EB ;
ROSENFELD, MG ;
EVANS, RM .
NATURE, 1985, 318 (6047) :635-641