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Understanding hypertension: A plausible link between biological clock and blood pressure

Aishwarya Segu

Researchers from the Central University of Jammu have uncovered a potential genetic link between the biological clock and hypertension in the Indian sub-population. They found that the biological clock plays a significant role in regulating hypertension, highlighting its importance as a risk factor for cardiovascular diseases in the ageing population.

Aishwarya Jan 2025 title image
A schematic representation showcasing connecting link between SNP's of CLOCK gene with EH. Picture credits Medha and Audesh Bhat.

Hypertension, a fatal asymptomatic condition with consistent high blood pressure is a widespread disorder affecting millions globally. It can arise as a secondary symptom due to issues like hormonal imbalances, apnea, pregnancy or kidney failure, and this type of hypertension is commonly known as secondary hypertension. Essential hypertension (EH), another subtype of hypertension, on the other hand, has no known causes and affects 90% of hypertensive patients. The origins of essential hypertension are complex, majorly involving genetic, environmental, and lifestyle factors. 

Most organisms, including humans, are influenced by the 24-hour day-night cycle (circadian rhythm), to which they synchronise their biological systems to the environmental cycle through a molecular clock. This clock is essential for regulating various physiological processes, including hypertension, says Audesh Bhat, Assistant Professor, Central University of Jammu.

Like a 24-hour clock, an internal clock consists of time-keeping mechanisms. These are genes and transcription factors. The human molecular clock is a core complex of CLOCK, PER, CRY and BMAL1 genes. In the recently published article in BMC Med Genomics, Bhat and others identified genetic correlations between circadian clock-regulating genes and EH. 

Bhat implies that certain ethnic groups are predisposed to having higher cases of hypertension. He believes that genetic variations play a critical role in these aspects. To explore this specifically in the population of Jammu, Bhat and others conducted a genetic correlation study involving 910 participants from Jammu, of whom 405 were identified with EH.

Audesh Bhat and his team. From left: Audesh Bhat, Shreya Sopari and Sonali Bhan. Picture Credit: Audesh Bhat.
Audesh Bhat and his team. From left: Audesh Bhat, Shreya Sopari and Sonali Bhan. Picture Credit: Audesh Bhat. 

The study focused on single nucleotide polymorphisms (SNPs) in the CLOCK and BMAL1 genes to examine the genetic correlation with hypertension. SNPs are variations wherein a single base in the gene genetic code is different, potentially altering gene function. The researchers discovered three SNPs known to be previously involved in EH. Two of which were strongly associated with EH in the population of Jammu. They found that an SNP in the 3′ untranslated region (UTR) of the CLOCK gene was positively correlated with hypertension, while an SNP in exon 9 showed a negative correlation, suggesting a protective role.

These results indicate that the CLOCK gene plays a significant role in the genetic predisposition to hypertension, potentially disrupting the body’s internal clock and contributing to blood pressure regulation issues. Bhat emphasises that ethnicity is a crucial factor in complex diseases like essential hypertension, noting that while his findings have been linked to hypertension in various genetically diverse populations, they have not yet been explored in any Indian population. This is the first report from any North Indian population and he believes these variants may also have a role in other Indian populations.

The study emphasises the importance of lifestyle changes that improve circadian rhythms, such as better sleep hygiene, avoiding shift work, and managing stress. These adjustments could be crucial for individuals with certain CLOCK gene variants, potentially helping reduce the genetic risk for hypertension. 

The association between CLOCK gene polymorphisms and hypertension in a North Indian population offers valuable insights into how our internal clocks may influence blood pressure regulation. These findings could lead to more targeted treatments and interventions. Shahnaz Rahman Lone, Assistant Professor, Gandhi Institute of Technology and Management (GITAM), Visakhapatnam, and an expert in Circadian Biology, cautions that the association with the CLOCK gene alone does not conclusively prove the involvement of circadian rhythms in hypertension. 

Bhat further stresses the need to identify diverse genetic risk factors and explore their correlations with diseases to deepen our understanding of the disorder. 

Lone adds that this is a well-conducted study; however, it represents only a small part of northern India. Further studies analysing other biological clock genes are necessary to better understand the role of the circadian system in hypertension. Bhat agrees and advocates for expanding these studies with larger sample sizes and greater collaborative research. 

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