Glucocorticoid receptor-9beta polymorphism is associated with systolic blood pressure and heart growth during early childhood. The Generation R Study.
Geelhoed JJM., van Duijn C., van Osch-Gevers L., Steegers EAP., Hofman A., Helbing WA., Jaddoe VWV.
BACKGROUND: glucocorticoid receptor-9β polymorphism (rs6198) is associated with the susceptibility for cardiovascular disease. AIM: to examine whether the GR-9 β 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-9β 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 mmHg (95% CI: 0.16, 5.14), an increased heart rate of 9.10 beats per minute (95% CI: 1.28, 16.7) and an increased left ventricular mass of 4.99 g (95% CI: 1.33, 8.65) compared to homozygous references. This means an increase of 2.6%, 8.6% and 16%, respectively. GR-9 β 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.