Influence of Genetic Admixture Components on CYP3A5*3 Allele-Associated Hypertension in Amerindian Populations From Northwest Mexico.

CYP3A5 metabolizes endogenous substrates and ~30% of prescription drugs. The CYP3A5 gene contains an active CYP3A5*1 allele, and a non-functional version, the CYP3A5*3 (rs776746), with consequences for drug therapeutic responses and side effects. Both CYP3A5*1 and *3 have been associated with hypertension. The frequency of CYP3A5*3 varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of CYP3A5*3 in drug response and hypertension development, the aim of the present study was to evaluate the frequency of this polymorphism and its association with hypertension in vulnerable indigenous populations in Mexico. A total of 372 subjects were recruited from eight ethnic groups in Northwest Mexico. Systolic (SBP), diastolic (DBP), and median (MBP) blood pressures as well as body mass index (BMI) were measured. Ancestry was evaluated through STR analysis, and the CYP3A5*1/*3 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of CYP3A5*1 and *3 were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The CYP3A5*3/*3 genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the *1 allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17-0.83, p = 0.001) and DBP (OR 0.38, 95% CI 0.18-0.81, p = 0.007) in women. This association remained significant after adjusting for BMI and age for diastolic (OR, 0.38; 95% CI, 0.17-0.84, p = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15-0.76, p = 0.005) BP levels in women. Thus, the frequency of CYP3A5*3 varies between groups and seems to depend on ancestry, and CYP3A5*1 decreases the risk of hypertension in Mexican indigenous women. This population analysis of CYP3A5*1/*3 has profound implications not only for the susceptibility to diseases, such as hypertension, but also for safer drug administration regimens, assuring better therapeutic responses and fewer side effects.

Influence of CYP1A1*2C on high triglyceride levels in female Mexican indigenous Tarahumaras.

BACKGROUND AND AIMS: High triglyceride levels are closely related to cardiovascular disease. Its development lays on age, diet, physical activity, ethnicity and genetic factors. Among the last, the CYP1A1*2C allele has an influence on the metabolism of cholesterol and other fatty acids. We undertook this study to determine the frequency of CYP1A1*2C and its association with triglyceride levels in Mexican indigenous Tarahumaras and Tepehuanos. METHODS: Anthropometric and biochemical data were recorded. Genotyping of CYP1A1*2C by RT-PCR was done in 110 Tepehuano, 69 Tarahumara and 64 Mestizo. RESULTS: Significant differences in age, waist diameter, BMI, creatinine, glucose, cholesterol, triglycerides, HDL and VLDL measurements were found between Tarahumaras and Tepehuanos (p <0.05). Additionally, Tarahumara women showed the highest values of waist diameter, BMI and triglycerides (p <0.05). It was found that Tarahumaras showed a significant association between high triglyceride levels and CYP1A1*2C allele (OR = 2.57; 95% CI 1.12-5.88, p = 0.024) under a recessive inheritance model. However, the Tepehuano group showed a significant protective association between normal triglyceride levels and CYP1A1*2C polymorphism (OR = 0.28; 95% CI 0.10-0.80, p = 0.015) following a dominant inheritance model. The same pattern was observed after analysis with females of both ethnicities. CONCLUSION: A significant association between CYP1A1*2C and high triglyceride levels in Amerindian Tarahumaras from Chihuahua has been found; this allele was significantly associated with normal triglyceride levels in Tepehuanos from Durango, Mexico. Further studies are needed to elucidate the genetic role of CYP1A1 in cardiovascular disease susceptibility.

Perception of the usefulness of drug/gene pairs and barriers for pharmacogenomics in Latin America.

Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.

Perfil de consumo de antibióticos en un hospital pediátrico de la ciudad de México / Antibiotics consumption in pediatric hospital in Mexico City

Antecedentes. El uso de antibióticos (ATB) representa una de las actividades más comunes que se llevan acabo en la práctica diaria. Objetivo. Determinar como se efectúa la distribución y consumo de los ATB en el Instituto Nacional de Pediatría (INP) por ser el grupo de fármacos de mayor interés terapéutico. Método. El análisis sobre la distribución y consumo de medicamentos se realizó directamente en la farmacia del hospital, en un período de 15 meses (de enero-1994 a marzo-95). Resultados. Se entregaron 406,773 medicamentos, encontrándose una mayor distribución hacia el servicio de infectología con 120,731 (29.6 por ciento), Medicina Interna 92,206 (22.6 por ciento). Del total de medicamentos distribuidos entre los servicios 130,627 (32.1 por ciento) correspondió al grupo de los ATB, llamando la atención el "consumo" de ATB en Cirugía con 63.0 por ciento, cantidad que superó significativamente el consumo de anestésicos en dicho servicio (p<0.05). Conclusiones. El perfil de consumo de medicamentos en el INP mostró tendencias al consumo excesivo de ATB. Además, una de las fallas detectadas para el uso adecuado de ATB en el Instituto fue que, no existe colaboración entre las Comisiones de Control de medicamentos con el Servicio de Farmacoología para que se norme y vigile el uso de los mismos, como una contribución del manejo racional de los ATB, y con ello evitar o disminuir sus consecuencias

Conceptos de farmacoquinecia útiles en la terapéutica neonatal / Concepts of pharmacokinetic in neonatal therapeutic

El uso de fármacos en niños, particularmente en neonatos, requiere del entendimiento de los procesos de enfermedad y del conocimiento actualizado de la farmacocinética y farmacodinámica de los medicamentos. En esta revisión se señalan los hechos más relevantes en cuanto a la absorción de los fármacos, su transporte a través de las membranas biológicas, su unión a las proteínas tisulares y plasmáticas, su biotransformación y su alimentación en el neonato y niños lactantes, haciendo énfasis en los factores que alteran estos procesos