Low frequency of CYP2D6 poor metabolizers among schizophrenia patients

Abstract

CYP2D6 has been suggested to be functionally similar to the dopamine transporter. The present study was aimed at analysing the frequency of CYP2D6 alleles and genotype among schizophrenic patients compared to healthy volunteers. CYP2D6 *3, *4, *5, *6, *10 and duplicated alleles were analysed in 128 unselected schizophrenia inpatients (SP) and 142 unrelated white European Spanish healthy volunteers (HV). SP and HV with 42, 2, 1 or 0 CYP2D6 active genes were 4.7, 64.8, 28.1 and 2.3%, and 6.3, 52.1, 33.1 and 8.5%, respectively. The frequency of homozygous for CYP2D6 inactive alleles or poor metabolizers (PMs) was lower (Po0.05) in SP than in HV. Furthermore, the frequency of CYP2D6 inactive alleles was also lower in SP than in HV (16.8 vs 25.7; Po0.05), specifically the CYP2D6*6 allele was not found among patients. The present study shows a lower frequency of PMs in schizophrenic patients than in healthy volunteers supporting the hypothesis of a potential role of CYP2D6 in the vulnerability to schizophrenia.

Influence of <i>CYP2D6</i> Deletion, Multiplication, <i>–1584C</i>→<i>G</i>, <i>31G</i>→<i>A</i> and <i>2988G</i>→<i>A</i> Gene Polymorphisms on Dextromethorphan Metabolism among Mexican Tepehuanos and Mestizos

“…The frequency of multiplication of functional genes of CYP2D6 in the Mestizo group was 4.1%, similar to that of Caucasians (3.9%) [22] , Mexican Americans (3%) [14] and Cubans (4.6%) [18] but lower than in Mestizo Mexicans (12.8%) [15] ( table 1 ). There has been no study concerning the determination of multiplication in Amerindians; in our Tepehuano Amerindian group, the frequency was of 1.5%, which is higher than the one observed in Asians (0.3%).…”

“…The frequency of allele * 5 in the Mestizo group (1.3%) was more similar to that of Spaniards (1.4%) [22] , Mexican Americans (1.7%) [13] and Colombians (0.8%) [17] . In the Tepehuano group, the frequency of this allele (0.5%) was much lower than those reported for Asian populations (4.5-6.2%) [28,29] and the Mapuche group of Chile (4.2%) [20] , while it has not been detected in Ngawbe and Embera of Panama and Colombia [19] .…”

CYP2D6 polymorphism in patients with eating disorders

“…12 Present findings seem to be in agreement with previous results showing that UMs are more frequent among suicide cases, 13 persistent mood-disordered patients 14 and among women with symptoms of depression, 15 which usually overlap with ED. [16][17][18] In addition, we have previously reported that PMs are less frequent among schizophrenic patients than among healthy subjects (2.3 vs 8.5%, respectively), 19 which would be in accordance with lower scores on a measure of risk to psychopathology or general distress also found among PM healthy volunteers. 11 Moreover, PMs seem to perform better on a cognitive task that assesses sustained attention, a trait characteristically impaired in patients with schizophrenia, bipolar depression and attention and deficit hyperactive disorder.…”

Xenobiotic-Metabolizing Enzymes and Transporters in the Normal Human Brain: Regional and Cellular Mapping as a Basis for Putative Roles in Cerebral Function

“…The lack of detection of CYP2E1 protein, even though high levels of CYP2E1 mRNA were present, could be explained by the rapid ubiquitination of the enzyme in the absence of substrates (Banerjee et al, 2000). CYP2D6 has been implicated in the metabolism of endogenous compounds such as anandamide (Snider et al, 2008) and neurotransmitters (Yu et al, 2003(Yu et al, , 2004) and reported as a risk factor in Parkinson's disease (Elbaz et al, 2004) and psychiatric disorders (Llerena et al, 2007). Finally, CYP1B1 is overexpressed in a variety of central nervous system malignancies, and increased CYP1B1 expression in glial tumors was associated with decreased patient survival (Barnett et al, 2007).…”