The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

Abstract Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β) globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of βS haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management

SLCO1A2, SLCO1B1 and SLCO2B1 polymorphisms influences chloroquine and primaquine treatment in Plasmodium vivax malaria

Financial support was provided by Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnologico (CNPq, Brazil)Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Para. Laboratório de Microbiologia e Imunologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Hospital de Clínicas de Porto Alegre. Unidade de Bioestatística. Grupo de Pesquisa e Pós Graduação. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Aim: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. Patients & methods: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. Results: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p FDR = 0.018 and p FDR = 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response. Conclusion: The present work presents the first pharmacogenetic report of an association between chloroquine/primaquine responses with OATP transporters

Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection

<div><p>Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals.</p></div

IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17A plasma levels in HIV-seronegative control and HIV-seropositive individuals grouped by different clinical stages of HIV infection.

<p>IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17A plasma levels in HIV-seronegative control and HIV-seropositive individuals grouped by different clinical stages of HIV infection.</p

Clinical baselines and demographic characteristics of the 41 HIV-infected subjects enrolled in this study as rapid or slow disease progressors.

<p>Clinical baselines and demographic characteristics of the 41 HIV-infected subjects enrolled in this study as rapid or slow disease progressors.</p

Flowchart of the sampling procedure.

<p>Flowchart of the sampling procedure.</p

SLCO1A2, SLCO1B1

Financial support was provided by Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnologico (CNPq, Brazil)Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Universidade Federal do Para. Laboratório de Microbiologia e Imunologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Ensaios Clínicos em Malária. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Genética Humana e Médica. Belém, PA, Brazil.Hospital de Clínicas de Porto Alegre. Unidade de Bioestatística. Grupo de Pesquisa e Pós Graduação. Porto Alegre, RS, Brazil.Universidade Federal do Rio Grande do Sul. Departamento de Genética. Porto Alegre, RS, Brazil.Aim: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. Patients & methods: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. Results: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p FDR = 0.018 and p FDR = 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response. Conclusion: The present work presents the first pharmacogenetic report of an association between chloroquine/primaquine responses with OATP transporters