CYP2C9 and VKORC1 polymorphisms are differently distributed in the Brazilian population according to self-declared ethnicity or genetic ancestry.

BACKGROUND: Warfarin-dosing pharmacogenetic algorithms have presented different performances across ethnicities, and the impact in admixed populations is not fully known. AIMS: To evaluate the CYP2C9 and VKORC1 polymorphisms and warfarin-predicted metabolic phenotypes according to both self-declared ethnicity and genetic ancestry in a Brazilian general population plus Amerindian groups. METHODS: Two hundred twenty-two Amerindians (Tupinikin and Guarani) were enrolled and 1038 individuals from the Brazilian general population who were self-declared as White, Intermediate (Brown, Pardo in Portuguese), or Black. Samples of 274 Brazilian subjects from Sao Paulo were analyzed for genetic ancestry using an Affymetrix 6.0(®) genotyping platform. The CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 g.-1639G>A (rs9923231) polymorphisms were genotyped in all studied individuals. RESULTS: The allelic frequency for the VKORC1 polymorphism was differently distributed according to self-declared ethnicity: White (50.5%), Intermediate (46.0%), Black (39.3%), Tupinikin (40.1%), and Guarani (37.3%) (p<0.001), respectively. The frequency of intermediate plus poor metabolizers (IM+PM) was higher in White (28.3%) than in Intermediate (22.7%), Black (20.5%), Tupinikin (12.9%), and Guarani (5.3%), (p<0.001). For the samples with determined ancestry, subjects carrying the GG genotype for the VKORC1 had higher African ancestry and lower European ancestry (0.14±0.02 and 0.62±0.02) than in subjects carrying AA (0.05±0.01 and 0.73±0.03) (p=0.009 and 0.03, respectively). Subjects classified as IM+PM had lower African ancestry (0.08±0.01) than extensive metabolizers (0.12±0.01) (p=0.02). CONCLUSIONS: The CYP2C9 and VKORC1 polymorphisms are differently distributed according to self-declared ethnicity or genetic ancestry in the Brazilian general population plus Amerindians. This information is an initial step toward clinical pharmacogenetic implementation, and it could be very useful in strategic planning aiming at an individual therapeutic approach and an adverse drug effect profile prediction in an admixed population.

Nutritional risk in the urban population of Ouro Preto, southeastern region of Brazil: the Ouro Preto heart study.

OBJECTIVE: To estimate the prevalence of combined nutritional risk according to sociodemographic and sedentarism characteristics of the urban population of Ouro Preto, state of Minas Gerais, Brazil. METHODS: This cross-sectional study was conducted with a probability sampling of 768 subjects aged 15 years or older. Nutritional risk (NR) was defined according to the BMI and WC classification criteria adopted by the National Institutes of Health. Isolated NR (INR) was defined as women with WC > 80 cm and men with WC > 94 cm, and the combined nutritional risk (CNR) as the same WC values mentioned above and/or BMI > 25 kg/m(2). Binary logistic regression and the Hosmer & Lemeshow test were used to construct and adjust these models. RESULTS: INR was observed in several BMI categories for both women and men, with the following results: 19.1% and 1.4% among those with normal weight, 91.7% and 56% in overweight patients, and 98.5% and 80% in obese patients, respectively. Age and level of education were independently associated with the CNR. Odds ratios (OR) for CNR in women and men over 60 years of age were 9.94 and 14.35, respectively, when compared to younger patients. For women with < 4 years of schooling, the OR was 1.83 compared to patients with more than 4 years of school attendance, while among men with an average number of years of school attendance, the OR was 2.55 relative to those with more years of schooling. CONCLUSION: These findings show that age and education have an independent effect on the probability of CNR occurrence, and also that a joint analysis of BMI and WC is important in screening groups for nutritional risk.

Circadian pattern of ventricular tachycardia episodes in patients with Chagas heart disease.

Chronic Chagas' cardiomyopathy (CCM) causes ventricular arrhythmias and sudden death, and constitutes the most frequent cause of death in many endemic areas. The circadian variation in the incidence of ventricular arrhythmias and sudden death differs according to the substrate (e.g., morning and evening peaks in ischemic heart disease and non-Chagasic dilated cardiomyopathy). Third generation implantable cardioverter defibrillators (ICDs) have the ability to store the time and date of each ventricular tachycardia (VT) episode, enabling the patterns of ventricular tachyarrhythmia occurrence to be analyzed. The aim of our study was to evaluate the circadian variation of spontaneous VT in recipients of an ICD with CCM.