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.
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.
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