The population of Brazil, formed by extensive admixture between Amerindians, Europeans and Africans, is one of the most variable in the world. We have recently published a study that used ancestry-informative markers to conclude that in Brazil, at an individual level, color, as determined by physical evaluation, was a poor predictor of genomic ancestry, estimated by molecular markers. To corroborate these findings we undertook the present investigation based on data from 12 commercially available forensic microsatellites that were utilized to estimate the personal genomic origin for each of 752 individuals from the city of São Paulo, belonging to different Brazilian color categories (275 Whites, 192 Intermediates and 285 Blacks). The genotypes permitted the calculation of a personal likelihood-ratio estimator of African or European ancestry. Although the 12 marker set proved capable of discriminating between European and African individuals, we observed very significant overlaps among the three color categories of Brazilians. This was confirmed quantitatively using a Bayesian analysis of population structure that did not demonstrate significant genetic differentiation between the three color groups. These results corroborate and validate our previous conclusions using ancestry-informative markers that in Brazil at the individual level there is significant dissociation of color and genomic ancestry.

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 ± 18.5, 37.6 ± 14.6, 34.8 ± 14.6, and 35.4 ± 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 ± 26.8, 48.0 ± 26.9, 48.1 ± 25.7, and 45.7 ± 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.

In families afflicted with haemophilia A, genetic counselling is often requested. Inversion mutations and polymorphic sites of the FVIII gene have been examined in a Brazilian population, with the aim of developing a strategy that would be accurate and informative for carrier analysis and prenatal diagnosis in Brazil. Patients with haemophilia A and families were studied. Inversion mutations in the FVIII gene were detected in 39.4% of severely affected patients, 85% of them being of distal type. No inversions were observed in patients with mild or moderate forms of the disease. Two bi-allelic polymorphisms were studied. Intron 18 SSCP and intron 19 RFLP analyses indicated the presence of a restriction site in 39.5% and 42.9% of haemophilics, respectively. Two multiallelic microsatellite polymorphisms in introns 13 and 22 were also studied; eight different alleles were detected in each system with a heterozygosity rate of 83.08% and 78.77%, respectively. When all four intragenic loci were examined in linkage analysis, the cumulative reliability was 100%. In conclusion, inversion mutation analysis should be the first-line test for Brazilian patients with severe haemophilia A. In cases of severe haemophilia A where no inversion could be detected or in mild or moderate haemophilia A, the use of all four polymorphisms is very informative for linkage analysis and should be used for carrier detection and genetic counselling in the Brazilian population.

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