Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• There is large interindividual variability in the pharmacokinetics of protease inhibitors (PIs) among human immunodeficiency virus (HIV)-infected individuals under highly active antiretroviral therapy. • Protease inhibitor have been recently reported to be substrates of the SLCO1B1/OATP1 drug transporter.• A single nucleotide polymorphism (SNP) in the SLCO1B1 gene (521T→C) was associated with plasma levels of lopinavir in HIV-infected individuals. WHAT THIS STUDY ADDS• Data on the impact of three SLCO1B1 SNPs (521T→C, 388A→G, 463C→A) on the trough plasma concentration of lopinavir and ritonavir in a cohort of 99 adult HIV-infected Brazilian men under stable highly active antiretroviral therapy.• Evidence that carriers of the 521C allele display significantly higher lopinavir, but not ritonavir plasma concentrations relative to the wild-type TT genotype.• No effect of either 388A→G or 463C→A SNPs on lopinavir or ritonavir plasma concentrations.• Further studies are required to confirm the clinical significance of the association between the SLCO1B1521T→C polymorphism and lopinavir pharmacokinetics. AIMSTo investigate possible associations between three SLCO1B1 single nucleotide polymorphisms (388A→G, 463C→A, 521T→C) and lopinavir/ritonavir plasma concentrations. METHODSThe study included 99 human immunodeficiency virus-infected men on stable highly active antiretroviral therapy containing lopinavir/ritonavir. Trough concentrations of lopinavir and ritonavir in plasma were quantified using liquid chromatography-tandem mass spectrometry. Genotyping of SLCO1B1388A→G, 463C→A and 521T→C polymorphisms was performed by allelic discrimination using real-time polymerase chain reaction. RESULTSThe trough concentration of lopinavir in plasma is significantly associated with SLCO1B1521T→C genotypes (P = 0.03). There is a significant trend for increasing concentrations of lopinavir from TT to TC to CC genotypes (P = 0.02). Carriers of the 521C allele display significantly higher lopinavir plasma concentrations relative to the wild-type TT genotype (P = 0.03). CONCLUSIONSReduced uptake of lopinavir by hepatocytes in carriers of the 521C allele may account for these results, but further studies to confirm the clinical importance of SLCO1B1 polymorphisms in lopinavir pharmacokinetics are warranted.British Journal of Clinical Pharmacology DOI:10.1111DOI:10. /j.1365DOI:10. -2125DOI:10. .2009 Br J Clin Pharmacol / 69:1 / 95-98 / 95

Obesity is a pandemic condition of complex etiology, resulting from the increasing exposition to obesogenic environmental factors combined with genetic susceptibility. In the past two decades, advances in genetic research identified variants of the leptin-melanocortin pathway coding for genes, which are related to the potentiation of satiety and hunger, immune system, and fertility. Here, we review cases of congenital leptin deficiency and the possible beneficial effects of leptin replacement therapy. In summary, the cases presented here show clinical phenotypes of disrupted bodily energy homeostasis, biochemical and hormonal disorders, and abnormal immune response. Some phenotypes can be partially reversed by exogenous administration of leptin. With this review, we aim to contribute to the understanding of leptin gene mutations as targets for obesity diagnostics and treatment strategies.

Data related to 15 short tandem repeat polymorphisms (STRPs) are reported for four South American Indian populations, and integrated with previous Brazilian Indian results. Overall heterozygosities varied significantly among groups (Kruskal-Wallis test, P = 0.002). The lowest levels of heterozygosity were observed in the Ache, Ayoreo, and Surui, an expected finding considering their isolation and ethnohistory. Genetic distance and gene diversity analyses suggested that geography was a good predictor of genetic affinity among these Native Americans. New evidence from this study supports the hypothesis that the Ache population descends from a Ge group that preceded the Guarani colonization of Paraguay.

Objectives: Clozapine is quite effective to treat schizophrenia, but its use is complicated by several factors. Although many patients respond to antipsychotic therapy, about 50% of them exhibit inadequate response, and ineffective medication trials may entail weeks of unremitted illness, potential adverse drug reactions, and treatment nonadherence. This review of the literature sought to describe the main pharmacogenetic studies of clozapine and the genes that potentially influence response to treatment with this medication in schizophrenics. Methods: We searched the PubMed database for studies published in English in the last 20 years using keywords related to the topic. Results and Conclusions: Our search yielded 145 studies that met the search and selection criteria. Of these, 21 review articles were excluded. The 124 studies included for analysis showed controversial results. Therefore, efforts to identify key gene mechanisms that will be useful in predicting clozapine response and side effects have not been fully successful. Further studies with new analysis approaches and larger sample sizes are still required.

The marked increase in STL heterogeneity as men age is consistent with a role for ALT during spermatogenesis. No data have yet reported the effect of age on STL heterogeneity. Based on these results, future studies should expand this modest sample size to search for molecular evidence of ALT in human testes during spermatogenesis.

Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment.

Our results suggest a role for CYP3A5 and DRD3 gene variants on refractoriness to neuroleptic treatment in Brazilians with schizophrenia.