Frequency of the Q192R and L55M polymorphisms of the human serum paraoxonase gene (PON1) in ten Amazonian Amerindian tribes

Human serum paraoxonase (PON1) is an esterase associated with high density lipoproteins (HDLs) in the plasma and may confer protection against coronary artery disease. Serum PON1 levels and activity vary widely among individuals and populations of different ethnic groups, such variations appearing to be related to two coding region polymorphisms (L55M and Q192R). Several independent studies have indicated that the polymorphism at codon 192 (the R form) is a significant risk factor for cardiovascular disease in some populations, although this association has not been confirmed in other populations. Given the possible associations of these mutations with heart diseases and the fact that little or nothing is known of their prevalence in Amerindian populations, we investigated the variability of both polymorphisms in ten Amazonian Indian tribes and compared the variation found with that of other Asian populations in which both polymorphisms have been investigated. The results show that the LR haplotype is the most frequent and the MR haplotype is absent in all Amerindians and Asian populations. We also found that South America Amerindians present the highest frequency of the PON1192*R allele (considered a significant risk factor for heart diseases in some populations) of all the Amerindian and Asian populations so far studied

<it>IL1B</it>, <it>IL4R</it>, <it>IL12RB1</it> and <it>TNF</it> gene polymorphisms are associated with <it>Plasmodium vivax</it> malaria in Brazil

Abstract Background Malaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood. Methods The present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test. Results The IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively). Conclusion Plasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.</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