CYP2D6 Pharmacogenetics Testing and Post-Cesarean Section Pain Scoresa Preliminary Study

被引:1
作者
Ribeiro, Carolina [1 ]
Quinta, Rosa [1 ]
Raposo, Ana [1 ]
Valentim, Ana [3 ]
Albuquerque, Jose [1 ]
Grazina, Manuela [1 ,2 ]
机构
[1] Univ Coimbra, Lab Biochem Genet, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal
[2] Univ Coimbra, Fac Med, Polo 3,Subunit 1, P-3000548 Coimbra, Portugal
[3] Coimbra Univ Hosp, CHUC EPE, Coimbra, Portugal
关键词
CYP2D6; Pain; Pharmacogenetics; Cesarean Section; Dopamine; Tyramine; Modulation of Pain; CYTOCHROME-P450; 2D6; GENETIC MODULATION; GENOTYPE; POLYMORPHISM; METAANALYSIS; METABOLISM; SEROTONIN; STRATEGY; EFFICACY; THERAPY;
D O I
10.1093/pm/pny033
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Objective Prospective observational study to analyze CYP2D6 pharmacogenetics in 55 Portuguese adult parturients undergoing elective cesarean section and to investigate the association between CYP2D6 alleles and pain score. Methods DNA was extracted from peripheral blood by standard methods. Genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number determination with TaqMan probes by real-time polymerase chain reaction (PCR). Allele duplications were confirmed (long PCR and PCR-restriction fragment length polymorphism). Theoretical metabolic profiles prediction was based on genetic data and activity scores. Association was investigated between genotypes and predicted phenotypes with pain scores. Statistical analysis was performed by using a (2) test, and significance was set at P<0.05. Results The percentage of poor, intermediate, extensive, and ultrarapid metabolizers found were 9%, 38%, 46%, and 7%, respectively. The results reveal a positive association between alleles *4, *10, and pain. Conclusions A positive association was found between predicted reduced or null activity of CYP2D6 and increased pain. It can be hypothesized that if CYP2D6 activity is reduced, tyramine metabolism will decrease, resulting in reduced formation of endogenous dopamine. Consequently, activation of the signal transduction pathways that controls pain and analgesic effect may be reduced, leading to an increase in pain. Therefore, we would recommend CYP2D6 genotyping to anticipate the needs for analgesia, which will help to adjust opioid dose and maximize clinical efficacy while reducing side effects.
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收藏
页码:359 / 368
页数:10
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