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Mean baseline HbA1c was high, indicating delayed initiation of insulin treatment. Blood pressure and lipids were suboptimally controlled. Insulin regimens varied between countries, changed little and resulted in similar HbA1c levels after 24 months.

To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever, 236 dengue fever and 236 asymptomatic infections were genotyped for 593 single nucleotide polymorphisms in 56 genes across the type 1 interferon response pathway as well as other important candidate genes. By single locus analysis comparing dengue hemorrhagic fever with dengue fever, 11 of the 51 markers with p<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when p<6 × 10−4). The JAK1 single nucleotide polymorphisms showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC-SIGN). An association between dengue hemorrhagic fever and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 interferon-stimulated gene expression in these patients.

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Recent pharmacogenomic studies have revealed significant interethnic differences in glutathione S-transferase (GST) allelic frequencies among various ethnic groups. Therefore, we have investigated GSTM1 (gene deletion), GSTT1 (gene deletion) and GSTP1 (rs1695) polymorphism frequencies in 3 Brazilian ethnic groups (n = 203). GSTM1 and GSTT1 polymorphism analyses were performed by multiplex polymerase chain reaction, and GSTP1 (rs1695) analysis was done by polymerase chain reaction restriction fragment length polymorphism. GSTM1– polymorphism frequency was 33.2%, while GSTT1 null (GSTT1–) was 30.2%. The valine GSTP1*B (rs1695) allele was present in 35.1% subjects, while the heterozygous form (isoleucine/valine) was the most prevalent genotype (46.6%). We found a statistically significant difference in genotype frequency among Amerindians versus Caucasians (p = 0.016) and among Amerindians versus African-Americans (p = 0.033). Considerable frequency variation was found in our study, even when compared with other studies showing phylogeographical heterogeneity to the genes studied in Brazilian populations.

Many parasite populations are difficult to sample because they are non-uniformly distributed between several host species and are often not easily collected from the living host, limiting sample size and possibly distorting the representation of the population. For the parasite Schistosoma mansoni, we investigated the use of the aggregated eggs found in the stool of infected individuals as a simple and representative sample. Previously, we demonstrated that microsatellite allele frequencies can be accurately estimated from pooled DNA of cloned S. mansoni adults, and we show here that genotyping parasite populations from reproductively isolated laboratory strains can be used to identify these specific populations based on characteristic patterns of allele frequencies, as observed by polyacrylamide gel electrophoresis and automated sequencer analysis of fluorescently labeled PCR products. In addition, microsatellites used to genotype aggregates of eggs collected from stools of infected individuals produced results consistent with the geographic distribution of the samples. Direct analysis of total stool eggs can be an important approach to questions of population genetics for this parasite by increasing the sample size to thousands per individual and reducing bias.

BackgroundN-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups.ResultsOverall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians.ConclusionsOur results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.

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