ABSTRACT
Alteration of monoaminergic neurotransmission has been implicated in the pathophysiology of mood disorders, and CYP2C9 enzyme activity has been shown to be modulated by serotonin in vitro. The present study was aimed at analysing the frequency of CYP2C9 alleles (*1, *2, *3) among patients suffering from major depressive disorder. In all, 70 such suffering psychiatric outpatients were studied. The CYP2C9 genotypes were determined by allele-specific PCR. The CYP2C9*3 allele frequency was higher (P<0.01) among the patients suffering from major depression than in a population of 89 schizophrenic patients (odds ratio=3.3) and 138 healthy volunteers (odds ratio=2.8). The results suggest that CYP2C9 genetic polymorphism may be related to a major depressive disorder due to an alteration in endogenous metabolism, although a linkage between CYP2C9 and some other gene related to depression cannot be ruled out.
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References
Dahl ML . Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clin Pharmacokinet 2002; 41: 453–470.
LLerena A, Edman G, Cobaleda J, Benítez J, Schalling D, Bertilsson L . Relationship between personality and debrisoquine hydroxylation capacity. Suggestion of an endogenous neuroactive substrate or product of the cytochrome P4502D6. Acta Psychiatr Scand 1993; 87: 23–28.
Martínez C, Agúndez JA, Gervasini G, Martín R, Benítez J . Tryptamine: a possible endogenous substrate for CYP2D6. Pharmacogenetics 1997; 7: 85–93.
Yu AM, Idle JR, Byrd LG, Krausz KW, Kupfer A, Gonzalez FJ . Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6. Pharmacogenetics 2003; 13: 173–181.
Miners JO, Birkett DJ . Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45: 525–538.
Gervasini G, Martínez C, Agúndez JA, Garcia-Gamito FJ, Benítez J . Inhibition of cytochrome P450 2C9 activity in vitro by 5-hydroxytryptamine and adrenaline. Pharmacogenetics 2001; 11: 29–37.
Facciola G, Hidestrand M, von Bahr C, Tybring G . Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. Eur J Clin Pharmacol 2001; 56: 881–888.
Yasar U, Lundgren S, Eliasson E, Bennet A, Wiman B, de Faire U et al. Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms. Biochem Biophys Res Commun 2002; 22: 25–28.
Daikh BE, Lasker JM, Raucy JL, Koop DR . Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C9. J Pharmacol Exp Ther 1994; 271: 1427–1433.
Rifkind AB, Lee C, Chang TK, Waxman DJ . Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Arch Biochem Biophys 1995; 320: 380–389.
Dai D, Zeldin DC, Blaisdell JA, Chanas B, Coulter SJ, Ghanayem BI et al. Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics 2001; 11: 597–607.
Adams PB, Lawson S, Sanigorski A, Sinclair AJ . Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996; 31: 157–161.
Dorado P, Berecz R, Norberto MJ, Yasar Ü, Dahl ML, LLerena A . CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers. Eur J Clin Phamacol 2003; 59: 221–225.
Llerena A, Dorado P, Berecz R, Gonzalez AP, Peñas-lledo EM . Effects of CYPZD6 and CYP2C9 genotypes on fluoxetine and norfluoxetine plasma concentrations during steady-state conditions. Eur J Clin Pharmacol 2003; submitted.
Dalton SO, Johansen C, Mellemkjaer L, Norgard B, Sorensen HT, Olsen JH . Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003; 163: 59–64.
de Abajo FJ, Rodriguez LA, Montero D . Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case–control study. BMJ 1999; 319: 1106–1109.
Acknowledgements
Financial support: This study was supported by a grant from the Spanish Ministry of Health (Instituto Carlos III, FIS 01/0699). R Berecz was supported by the Hungarian–Spanish Intergovernmental Scientific and Technology Cooperation project (E-45/2001).
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LLerena, A., Berecz, R., Dorado, P. et al. CYP2C9 gene and susceptibility to major depressive disorder. Pharmacogenomics J 3, 300–302 (2003). https://doi.org/10.1038/sj.tpj.6500197
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DOI: https://doi.org/10.1038/sj.tpj.6500197
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