Endocrine Abstracts (2012) 28 P205

Circadian clock gene BMAL1 is associated with blood pressure but not autonomic function in man

Ida Pernicova1, Madhu Prasai1, Azhar Maqbool2, West Robert3, David A.S.G. Mary2 & Eleanor Scott1

1Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics Health and Therapeutics, LIGHT Laboratories, University of Leeds, Leeds, United Kingdom; 2Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics Health and Therapeutics, LIGHT Laboratories, University of Leeds, Leeds, United Kingdom; 3Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom; 4Department of Endocrinology, William Harvey Institute, London, United Kingdom.

Introduction: The circadian clock controls numerous aspects of mammalian physiology across the 24 hour day. The suprachiasmatic nucleus (SCN) is the “master clock” which coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Murine studies have shown a role for the core clock gene BMAL1 in the regulation of blood pressure. Selected haplotypes of BMAL1 have previously been associated with hypertension and diabetes in a family study. The aim of the present study was to investigate the relationship of BMAL1 SNP rs6486121 to blood pressure and sympathetic nerve activity in man.

Methods: 172 subjects with a wide range of blood pressure, comprising 85 normal subjects and 87 with untreated essential hypertension, were examined. Resting muscle sympathetic nerve activity was quantified by microneurography from multiunit bursts as a measure of efferent sympathetic nerve activity descending from the central nervous system. BMAL1 SNP rs6486121 was genotyped from DNA extracted from leucocytes.

Results: Adjusting for age and waist circumference homozygous possession of the minor C-allele of rs6486121 was associated with a higher mean systolic blood pressure (155 vs 144 mMHg; P=0.009). There was no statistically significant association with diastolic blood pressure or sympathetic nerve activity.

Conclusion: This work provides evidence, supporting previous work, that genetic variation in BMAL1 is associated with the development of hypertension in man. Whilst the mechanism of endogenous hypertension remains not completely understood, the lack of an association between BMAL1 and sympathetic nerve activity may suggest that circadian control of blood pressure is mediated predominantly through endocrine rather than autonomic mechanisms and this deserves further investigation.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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