Unraveling the Role of COMT Polymorphism in Dopamine-Mediated Vasopressor Effects: An Observational Cross-Sectional Study

Kannan Sridharan; Anfal Jassim; Ali Mohammed Qader; Sheikh Abdul Azeez Pasha

doi:10.2174/0113892002293952240315064943

Unraveling the Role of COMT Polymorphism in Dopamine-Mediated Vasopressor Effects: An Observational Cross-Sectional Study

Curr Drug Metab. 2024 Mar 20. doi: 10.2174/0113892002293952240315064943. Online ahead of print.

Authors

Kannan Sridharan¹, Anfal Jassim², Ali Mohammed Qader³, Sheikh Abdul Azeez Pasha⁴

Affiliations

¹ Department of Pharmacology & Therapeutics, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
² Department of Molecular Medicine, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
³ Salmaniya Medical Complex, Manama, Kingdom of Bahrain.
⁴ Adult intensive care unit, Salmaniya Medical Complex, Manama, Kingdom of Bahrain.

PMID: 38509678
DOI: 10.2174/0113892002293952240315064943

Abstract

Aims: To evaluate the association between rs4680 polymorphism in the COMT gene and the vasoconstrictive effects of commonly used vasopressors.

Background: Dopamine is a medication that is given intravenously to critically ill patients to help increase blood pressure. Catechol O-Methyl Transferase (COMT) breaks down dopamine and other catecholamines. There is a genetic variation in the COMT gene called rs4680 that can affect how well the enzyme works. Studies have shown that people with this genetic variation may have different blood pressure levels. However, no one has looked at how this genetic variation affects the way dopamine works to increase blood pressure.

Objectives: To investigate the impact of the rs4680 polymorphism in the COMT gene on the pharmacodynamic response to dopamine.

Methods: Critically ill patients administered dopamine were included following the consent of their legally acceptable representatives. Details on their demographic characteristics, diagnosis, drug-related details, changes in the heart rate, blood pressure, and urinary output were obtained. The presence of rs4680 polymorphism in the COMT gene was evaluated using a validated method.

Results: One hundred and seventeen patients were recruited, and we observed a prevalence of rs4680 polymorphism in 57.3% of our critically ill patients. Those with mutant genotypes were observed with an increase in the median rate of change in mean arterial pressure (mm Hg/hour) [wild: 8.9 (-22.6 to 49.1); heterozygous mutant: 5.9 (-34.1 to 61.6); and homozygous mutant: 19.5 (-2.5 to 129.2)] and lowered urine output (ml/day) [wild: 1080 (21.4 to 5900); heterozygous mutant: 380 (23.7 to 15800); and homozygous mutant: 316.7 (5.8 to 2308.3)].

Conclusion: V158M (rs4680) polymorphism is widely prevalent in the population and was significantly associated with altered effects as observed clinically. This finding suggests valuable insights into the molecular basis of COMT function and its potential impact on neurotransmitter metabolism and related disorders. Large-scale studies delineating the effect of these polymorphisms on various vasopressors are the need of the hour.

Keywords: COMT; SNP; critically ill.; dopamine; vasopressors.