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Current Drug Metabolism

Author(s): Kannan Sridharan*, Anfal Jassim, Ali Mohammed Qader and Sheikh Abdul Azeez Pasha

DOI: 10.2174/0113892002293952240315064943

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

Page: [152 - 156] Pages: 5

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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.

Graphical Abstract

[1]
Sridharan, K.; Hasan, H.; Al Jufairi, M.; Al Daylami, A.; Abdul Azeez Pasha, S.; Al Ansari, E. Drug utilisation in adult, paediatric and neonatal intensive care units, with an emphasis on systemic antimicrobials. Anaesthesiol. Intensive Ther., 2021, 53(1), 18-24.
[http://dx.doi.org/10.5114/ait.2021.103628] [PMID: 33625820]
[2]
Farzam, K.; Kidron, A.; Lakhkar, A.D. Adrenergic drugs. In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2022.
[3]
Lotta, T.; Vidgren, J.; Tilgmann, C.; Ulmanen, I.; Melén, K.; Julkunen, I.; Taskinen, J. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: A revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry, 1995, 34(13), 4202-4210.
[http://dx.doi.org/10.1021/bi00013a008] [PMID: 7703232]
[4]
Rs4680. Reference SNP report. dbSNP short genetic variations. Available from: https://www.ncbi.nlm.nih.gov/snp/rs4680 (Accessed on 29 March 2023).
[5]
Stroth, S.; Reinhardt, R.K.; Thöne, J.; Hille, K.; Schneider, M.; Härtel, S.; Weidemann, W.; Bös, K.; Spitzer, M. Impact of aerobic exercise training on cognitive functions and affect associated to the COMT polymorphism in young adults. Neurobiol. Learn. Mem., 2010, 94(3), 364-372.
[http://dx.doi.org/10.1016/j.nlm.2010.08.003] [PMID: 20800689]
[6]
Ma, J.; Zhao, M.; Zhou, W.; Li, M.; Huai, C.; Shen, L.; Wang, T.; Wu, H.; Zhang, N.; Zhang, Z.; He, L.; Qin, S. Association between the COMT Val158Met polymorphism and antipsychotic efficacy in schizophrenia: An updated meta-analysis. Curr. Neuropharmacol., 2021, 19(10), 1780-1790.
[http://dx.doi.org/10.2174/1570159X18666201023154049] [PMID: 33100205]
[7]
Lie, M.U.; Winsvold, B.; Gjerstad, J.; Matre, D.; Pedersen, L.M.; Heuch, I.; Zwart, J.A.; Nilsen, K.B. The association between selected genetic variants and individual differences in experimental pain. Scand. J. Pain, 2021, 21(1), 163-173.
[http://dx.doi.org/10.1515/sjpain-2020-0091] [PMID: 33108341]
[8]
Hussain, T.; Lokhandwala, M.F. Renal dopamine receptors and hypertension. Exp. Biol. Med., 2003, 228(2), 134-142.
[http://dx.doi.org/10.1177/153537020322800202] [PMID: 12563019]
[9]
Sonne, J.; Goyal, A.; Lopez-Ojeda, W. Dopamine. In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2022.
[10]
Patel, G.P.; Grahe, J.S.; Sperry, M.; Singla, S.; Elpern, E.; Lateef, O.; Balk, R.A. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock, 2010, 33(4), 375-380.
[http://dx.doi.org/10.1097/SHK.0b013e3181c6ba6f] [PMID: 19851126]
[11]
Suzuki, R.; Uchino, S.; Sasabuchi, Y.; Kawarai Lefor, A.; Sanui, M. Dopamine use and its consequences in the intensive care unit: A cohort study utilizing the Japanese Intensive care Patient Database. Crit. Care, 2022, 26(1), 90.
[http://dx.doi.org/10.1186/s13054-022-03960-y] [PMID: 35366934]
[12]
Marik, P. Low-dose dopamine: A systematic review. Intensive Care Med., 2002, 28(7), 877-883.
[http://dx.doi.org/10.1007/s00134-002-1346-y] [PMID: 12122525]
[13]
Holmes, C.L.; Walley, K.R. Bad medicine. Chest, 2003, 123(4), 1266-1275.
[http://dx.doi.org/10.1378/chest.123.4.1266] [PMID: 12684320]
[14]
Ge, L.; Wu, H.Y.; Pan, S.L.; Huang, L.; Sun, P.; Liang, Q.H.; Pang, G.F.; Lv, Z.P.; Hu, C.Y.; Liu, C.W.; Zhou, X.L.; Huang, L.J.; Yin, R.X.; Peng, J.H. COMT Val158Met polymorphism is associated with blood pressure and lipid levels in general families of Bama longevous area in China. Int. J. Clin. Exp. Pathol., 2015, 8(11), 15055-15064.
[PMID: 26823844]
[15]
Egan, M.F.; Goldberg, T.E.; Kolachana, B.S.; Callicott, J.H.; Mazzanti, C.M.; Straub, R.E.; Goldman, D.; Weinberger, D.R. Effect of COMT Val 108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci., 2001, 98(12), 6917-6922.
[http://dx.doi.org/10.1073/pnas.111134598] [PMID: 11381111]
[16]
Worda, C.; Sator, M.O.; Schneeberger, C.; Jantschev, T.; Ferlitsch, K.; Huber, J.C. Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women. Hum. Reprod., 2003, 18(2), 262-266.
[http://dx.doi.org/10.1093/humrep/deg059] [PMID: 12571159]
[17]
Htun, N.C.; Miyaki, K.; Song, Y.; Ikeda, S.; Shimbo, T.; Muramatsu, M. Association of the catechol-O-methyl transferase gene Val158Met polymorphism with blood pressure and prevalence of hypertension: Interaction with dietary energy intake. Am. J. Hypertens., 2011, 24(9), 1022-1026.
[http://dx.doi.org/10.1038/ajh.2011.93] [PMID: 21776034]
[18]
Hagen, K.; Pettersen, E.; Stovner, L.; Skorpen, F.; Holmen, J.; Zwart, J. High systolic blood pressure is associated with Val/Val genotype in the catechol-o-methyltransferase gene. Am. J. Hypertens., 2007, 20(1), 21-26.
[http://dx.doi.org/10.1016/j.amjhyper.2006.05.023] [PMID: 17198907]
[19]
Helkamaa, T.; Männistö, P.T.; Rauhala, P.; Cheng, Z.J.; Finckenberg, P.; Huotari, M.; Gogos, J.A.; Karayiorgou, M.; Mervaala, E.M. Resistance to salt-induced hypertension in catechol-O-methyltransferase-gene-disrupted mice. J. Hypertens., 2003, 21(12), 2365-2374.
[http://dx.doi.org/10.1097/00004872-200312000-00026] [PMID: 14654758]