M. Alvarez

Relation between CYP2D6 phenotype and genotype and personality in healthy volunteers

OBJECTIVESnOur group has previously show that interindividual variability in CYP2D6 hydroxylation capacity was related to personality differences in cognitive social anxiety. Thus, we aimed to analyze whether this relationship between personality and CYP2D6 phenotype and genotype was found in a similar population of healthy volunteers from a different latitude and culture by using the same methodology.nnnMETHODSnA total of 253 university students and staff from Havana Psychiatric Hospital and Calixto García Medical School in Cuba completed the Karolinska Scales of Personality (KSP), and were evaluated on debrisoquine hydroxylation capacity and CYP2D6 genotypes. KSP scores were compared between four groups, divided according to their CYP2D6 metabolic capacity: one of poor and three of extensive metabolizers. Furthermore, KSP scores were compared between another four different groups divided according to their number of CYP2D6 active genes: zero, one, two, and more than two.nnnRESULTSnIn Cubans, the differences in cognitive social anxiety-related personality traits across the four CYP2D6 hydroxylation capacity groups were strikingly similar to those found in Spaniards. These differences also came out to be significant for psychic anxiety (p = 0.02) and socialization (p = 0.02). The same pattern of results obtained for the subscales of psychic anxiety, socialization, psychasthenia and inhibition of aggression with regard to phenotype in both the Cuban and Spanish studies were seen with regard to CYP2D6 genotypes.nnnCONCLUSIONSnCorroborating these results further strengthens evidence of the relationship between CYP2D6 metabolic capacity and personality. In this population of healthy Cuban volunteers, the CYP2D6 hydroxylation capacity was related to the degree of anxiety and socialization. These results support the postulated reduction of serotonin in CYP2D6 poor metabolizers, which may be associated with a cluster of behavioral traits (e.g., anxiety, impulsivity). Thus, research is warranted to determine CYP2D6 functional implications for interindividual differences in vulnerability to neuropsychiatric diseases and drug response.

CYP2D6 -1584C>G promoter polymorphism and debrisoquine ultrarapid hydroxylation in healthy volunteers

BACKGROUND & AIMnThe CYP2D6 -1584C>G polymorphism (rs1080985) has been identified as a major factor for CYP2D6 expression and function, with the mutant -1584G promoter type being consistently associated with significantly greater expression than -1584C. It may therefore be associated with ultrarapid metabolism. The objective of the present study was to explore the relationship between the CYP2D6 -1584C>G polymorphism and the debrisoquine metabolic ratio in healthy volunteers in order to evaluate its potential impact on the ultrarapid CYP2D6 hydroxylation capacity.nnnMATERIALS & METHODSnThe CYP2D6 -1584C>G polymorphism was analyzed in 320 unrelated healthy individuals who were previously phenotyped for debrisoquine hydroxylation.nnnRESULTSnThe metabolic ratio (log10 mean ± standard deviation) of individuals with the -1584G allele was lower than that of individuals with the -1584C allele for carriers of one active CYP2D6 gene (-0.13 ± 0.33 and 0.17 ± 0.52, respectively; p < 0.05) or two active CYP2D6 genes (-0.32 ± 0.39 and -0.20 ± 0.44, respectively; p < 0.05).nnnCONCLUSIONnThe presence of the -1584G allele in the promoter region of the CYP2D6 gene was related to a high CYP2D6 hydroxylation capacity.

Estudio farmacogenético del polimorfismo metabólico de la debrisoquina (CYP2D6) en la población cubana en relación con la española

Fundamento y objetivo La capacidad metabolica del CYP2D6 presenta polimorfismo genetico. A partir del calculo del indice metabolico (IM) urinario de un farmaco test como la debrisoquina se ha demostrado la existencia de 2 fenotipos metabolicos: metabolizadores lentos y rapidos, entre los que hay un subgrupo de ultrarrapidos. El objetivo de este trabajo ha sido evaluar las diferencias interetnicas del polimorfismo metabolico de hidroxilacion de debrisoquina en la poblacion cubana, y compararla con la espanola. Pacientes y metodo El IM se evaluo en 260 voluntarios sanos cubanos (divididos en blancos y mestizos) que se compararon con 925 voluntarios sanos espanoles. Resultados La frecuencia de metabolizadores lentos fue similar entre cubanos y espanoles (un 4,6 y un 4,9%, respectivamente). Sin embargo, la prevalencia de metabolizadores ultrarrapidos fue menor en cubanos (3,8%) que en espanoles (5,2%). El IM en metabolizadores rapidos fue mayor (pxa0 Conclusiones Se observan diferencias interetnicas en el polimorfismo genetico del CYP2D6 en la poblacion cubana y en la frecuencia de metabolizadores ultrarrapidos respecto a los espanoles. Estas diferencias podrian condicionar en la poblacion cubana una variabilidad interindividual e interetnica en la respuesta a los farmacos sustratos del CYP2D6.

Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA Consortium Report on Population Pharmacogenomics

Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their predicted drug metabolism phenotypes across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews. Moreover, Native Americans were grouped into North-, Central-, and South Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic variants, and grouped as genotype-predicted poor or ultrarapid metabolizer phenotypes (gPMs and gUMs, respectively). Native Americans showed differences from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19. Native Americans had higher frequencies of wild-type alleles for all genes, and lower frequency of CYP2D6*41, CYP2C9*2, and CYP2C19*17 (pu2009<u20090.05). Native Americans also showed less CYP2C19 gUMs than the rest of the population sample. In addition, differences within Native Americans (mostly North vs. South) were also found. The interethnic differences described supports the need for population-specific personalized and precision medicine programs for Native Americans. To the best of our knowledge, this is the largest study carried out in Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9, and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field of global health and warrants further research and education.

Characterizing the variability of Melotte 111 AV 1224: a new variable star in the Coma Berenices open cluster

A search for new pulsating stars in the Coma Berenices open cluster was carried out. As a result of this search the cluster member Melotte 111 AV 1224 presented clear indications of photometric variability. In order to determine its physical parameters Stromgren standard indices and low-resolution spectra were acquired. In this work we present the preliminary results of these observations.

Strömgren Photometry of the Delta Scuti Stars 7 Aql and 8 Aql

The preliminary results of new photometric observations of the δ Scuti stars 7 Aql and 8 Aql are reported. 51 hr of uvby—β photoelectric photometric data were obtained over the period June and July 2007 at the San Pedro Martir Observatory, Mexico. Period analyses confirm the three pulsation modes discovered in 8 Aql in the framework of the STEPHI 2003 multisite campaign. For the star 7 Aql we were able to detect only the main pulsation modes. The standard magnitudes of both stars are obtained. The frequency, amplitude and phases of the frequency modes in different filters are presented.

CCD Photometry of the Pleiades Delta Scuti Star V650 Tauri

The preliminary results of a three-site CCD photometric campaign are reported. The

Physical parameters determination of the RR Lyrae Star a CM, SW, SZ and UY in Bootes

delta

CCD Photometry of Delta Scuti stars 7 Aql and 8 Aql

Scuti variable V650 Tauri belonging to the Pleiades cluster was observed photometrically for 14 days on three continents during 2008 November. An overall run of 164 hr of data was collected. At least five significant frequencies for V650 Tauri have been detected.

Activity as the Main Explanation of Light Variations of o And — Towards a Rotational Modulation Model

In this preliminary work, the determination of physical parameters for the RR Lyrae stars CM, SW, SZ, and UY in Bootes from Stromgren uvby-beta photometry is presented.