Izaura Cayres-Vallinoto

IFNG +874T/A polymorphism and cytokine plasma levels are associated with susceptibility to Mycobacterium tuberculosis infection and clinical manifestation of tuberculosis

Regarding the importance of interferon-gamma (IFN-gamma) in protective immunity against Mycobacterium tuberculosis and the functional role of IFNG +874T/A single nucleotide polymorphism (SNP) in the IFN-gamma production, the present study investigated the relationship of this genetic polymorphism with susceptibility to tuberculosis (TB). A total of 129 patients with pulmonary tuberculosis (PTB), 33 with extrapulmonary tuberculosis (EPTB), and 156 control subjects were studied. Blood samples were drawn and plasma was used to measure IFN-gamma serum concentration by enzyme-linked immunoassay. DNA samples were extracted from leukocytes and used to investigate +874T/A polymorphism in IFNG gene using allele-specific oligonucleotide-polymerase chain reaction. An association between the presence of the allele +874A and the genotype +874AA with the active tuberculosis was found (p < 0.0001, 95% confidence interval = 1.64-3.22), at the same time that allele + 874T and genotype +874T/T were more frequent in the control group. The average plasma concentration of IFN-gamma among patients with tuberculosis was significantly lower than in the control group, and were lower in the EPTB group than in the group with PTB, suggesting a relationship of low plasma levels of this cytokine with active tuberculosis and the progression to more serious forms of the disease. Furthermore, we observed the association of the +874T/T and +874A/A genotypes with high and low IFN-gamma plasma concentrations, respectively, both in TB patients and in the control groups. Thus our findings suggest an association of the IFNG +874T/A polymorphism with susceptibility to M. tuberculosis infection in the studied population.

Prevalence of infection by JC and BK polyomaviruses in kidney transplant recipients and patients with chronic renal disease

E.P. Pires, C.V. Bernardino‐Vallinoto, D.M. Alves, S.R.C. Migone, L.F.A. Machado, M.O.G. Ishak, R. Ishak, I.M.V. Cayres‐Vallinoto, A.C.R. Vallinoto. Prevalence of infection by JC and BK polyomaviruses in kidney transplant recipients and patients with chronic renal disease.
Transpl Infect Dis 2011: 13: 633–637. All rights reserved

Genetical-demographic data from two amazonian populations composed of descendants of african slaves: Pacoval and Curiau

The Amazon region of Brazil includes communities founded by escaped slaves, some of which still remain relatively isolated. We studied two such Afro-Brazilian communities (Pacoval and Curiau), in the rural area of Alenquer, Para, and in the metropolitan region of Macapa, Amapa, respectively. Among 12 blood loci, alleles considered as markers of African ancestry, such as HBB*S, HBB*C, TF*D1, HP*2M, ABO*B, RH*D-, and CA2*2 were found at frequencies that are expected for populations with a predominantly African origin. Estimates of interethnic admixture indicated that the degree of the African component in Curiau (74%) is higher than that of Pacoval (44%); an Amerindian contribution was not detected in Curiau. Estimated values of African ancestry fit well with the degree of isolation and mobility of the communities. Pacoval exhibited a high proportion of immigrants among the parents and grandparents of the individuals studied, whereas persons living in Curiau exhibited a low level of mobility, despite its location in the metropolitan area of Macapa city, suggesting a relatively strong barrier against the interethnic admixture in this population. In addition, analysis of genetic data in a sub-sample consisting of individuals whose parents and grandparents were born in the study site, and that probably represents the populations two generations ago, indicated that gene flow from non-black people is not a recent event in both populations.

Heterogeneity of Y chromosome markers among Brazilian Amerindians

The allele frequency distribution of DYS19 and DYS199 loci were analyzed in 59 Brazilian Amerindians from five tribes from the Amazon region (Zoé, Awá‐Guajá, Urubú‐Kaapór, Katuena, and Kayapó, Xikrin of Bacajá village). Three different alleles of the DYS19 microsatellite (182‐bp, 186‐bp, and 190‐bp) were found at average frequencies of 0.08, 0.85, and 0.07, respectively. The DYS199‐T allele was identified in 78% of the Amerindians studied (43/55), the frequencies varying from 0.46–0.93. Four different haplotypes were found, the combination DYS19–186/DYS199‐T being the most common (average frequency of 0.65), followed by DYS19–186/DYS199‐C with an average frequency of 0.22. These four haplotypes have been found in five other Brazilian tribes, and most of them were also identified in Native populations from South, Central and North America. The observed variability at the DYS19 microsatellite is probably due to forward or back mutations from the putative ancestral 186‐bp allele, since the mutation rate of this locus is high and the post‐Columbian admixture of the Brazilian tribes studied is very low or undetectable to explain these data. On the other hand, the DYS19/DYS199 haplotype distribution may suggest that the two most common haplotypes (186‐bp/T and 186‐bp/C) were present among the population(s) that peopled the New World. Am. J. Hum. Biol. 11:481–487, 1999.

FAS −670A/G single nucleotide polymorphism may be associated with human T lymphotropic virus-1 infection and clinical evolution to TSP/HAM

FAS and FASLG genes are closely linked to the apoptosis mechanism of the immune system and several polymorphisms in these genes have been associated with susceptibility to diseases. The present study investigated the polymorphisms at positions -670 in the FAS gene, and -169 and -124 in the FASLG gene, among HTLV-1 infected subjects. Blood samples from HTLV infected subjects and seronegative individuals were collected, and polymorphisms were analyzed using a polymerase chain reaction (PCR) followed by RFLP analysis using restriction endonucleases. The genotype frequencies of the FAS -670 polymorphism was the only one that showed a higher and significant prevalence of genotype -670GG among HTLV-1 infected subjects as compared to the control group (p=0.0160), but the genotype -670AA was more frequent among TSP/HAM patients as compared to the asymptomatic individuals (p=0.0005). TCD4(+) and TCD8(+) lymphocyte counts from HTLV infected and seronegative subjects, as well as the proviral load values, according to the status of symptomatic and asymptomatic infection carrying different genotypes were compared but showed no statistical significance. The present results suggest that FAS -670 polymorphism seems to be associated with susceptibility to HTLV-1 and may increase the chance to develop TSP/HAM among HTLV-1 infected persons.

Characterization of mannose-binding lectin plasma levels and genetic polymorphisms in HIV-1-infected individuals

INTRODUCTION The present study investigated the association between mannose-binding lectin (MBL) gene polymorphism and serum levels with infection by HIV-1. METHODS Blood samples (5 mL) were collected from 97 HIV-1-infected individuals resident in Belém, State of Pará, Brazil, who attended the Special Outpatient Unit for Infections and Parasitic Diseases (URE-DIPE). CD4+ T-lymphocyte count and plasma viral load were quantified. A 349bp fragment of exon 1 of the MBL was amplified via PCR, using genomic DNA extracted from controls and HIV-1-infected individuals, following established protocols. MBL plasma levels of the patients were quantified using an enzyme immunoassay kit. RESULTS Two alleles were observed: MBL*O, with a frequency of 26.3% in HIV-1-infected individuals; and the wild allele MBL*A (73.7%). Similar frequencies were observed in the control group (p > 0.05). Genotype frequencies were distributed according to the Hardy-Weinberg equilibrium in both groups. Mean MBL plasma levels varied by genotype, with statistically significant differences between the AA and AO (p < 0.0001), and AA and OO (p < 0.001) genotypes, but not AO and OO (p = 0.17). Additionally, CD4+ T-lymphocytes and plasma viral load levels did not differ significantly by genotype (p > 0.05). CONCLUSIONS The results of this study do not support the hypothesis that MBL gene polymorphism or low plasma MBL concentrations might have a direct influence on HIV-1 infection, although a broader study involving a large number of patients is needed.

No evidence of association between MBL2A/O polymorphisms and Mycobacterium tuberculosis infection in populations from the Brazilian Amazon region

The present study investigated the prevalence of the polymorphisms in the exon 1 of the MBL2 gene in patients with tuberculosis at a hospital in northern Brazil, which is a regional reference for the treatment of the disease. The study group was composed of 167 patients with tuberculosis, 34 of which had the extra-pulmonary form of the disease, while the other 133 had the pulmonary type. The control group consists of 159 healthy individuals. Samples of DNA extracted from leucocytes were submitted to Polymerase Chain Reaction for the amplification of a 120-bp segment of exon 1 of the MBL2 gene. The distribution of allele and genotype frequencies varied little among the different groups, and it was not possible to establish any clear association between the variants of the MBL2 gene and the susceptibility to or clinical profile of tuberculosis infections in the population analyzed.

Prevalence and risk behaviour for human immunodeficiency virus 1 infection in Marajó Island, Northern Brazil.

Abstract Background: Human immunodeficiency virus 1 (HIV-1) infection is a global public health problem, but, so far, there is no published information regarding the epidemiology of HIV-1 in Marajó Archipelago (Pará, Brazil). Aim: The present study reports the occurrence of infection by HIV-1 in four municipalities of the Marajó Island, Pará, Brazil. Subjects and methods: A total of 1877 samples were collected from volunteer blood donors (1296 women and 551 men) living in the municipalities of Anajás, Chaves, Portel and São Sebastião da Boa Vista. Information about risk behaviour assessment was obtained from a questionnaire. Plasma samples were tested for the presence of anti-HIV antibodies using serological tests. The infection was confirmed by nucleic acid amplification assays. Results: Twelve samples were seropositive for HIV by ELISA. Western blot analysis showed four positive samples, eight indeterminate patterns and one found to be negative. Molecular analysis revealed three positive samples. Risk factors for HIV-1 infection included absence of condoms during sexual intercourse (41.3%, São Sebastião da Boa Vista), use of illicit drugs (5.8%, Anajás) and early initiation of sexual activities, from 10–15 years (30.7%). Conclusion: Although the study indicates a low HIV-1 prevalence in Marajó Island, some factors may increase the risk for HIV-1 and these include early sexual initiation, unprotected sexual intercourse and the use of illicit drugs.

Human JCV Infections as a Bio-Anthropological Marker of the Formation of Brazilian Amazonian Populations

JC polyomavirus (JCV) is a member of the Polyomaviridae family. It presents a tropism to kidney cells, and the infection occurs in a variety of human population groups of different ethnic background. The present study investigated the prevalence of JCV infection among human populations from the Brazilian Amazon region, and describes the molecular and phylogenetic features of the virus. Urine samples from two urban groups of Belém (healthy subjects), one Brazilian Afro-descendant “quilombo” from the Rio Trombetas region, and native Indians from the Wai-Wai, Urubu-Kaapor, Tembé, Assurini, Arara do Laranjal, Aukre, Parakanã, Surui and Munduruku villages were investigated for the presence of the virus by amplifying VP1 (230 bp) and IG (610 bp) regions using a polymerase chain reaction. Nucleotide sequences (440 nucleotides, nt) from 48 samples were submitted to phylogenetic analysis. The results confirmed the occurrence of types A (subtype EU), B (subtypes Af-2, African and MY, Asiatic) and C (subtype Af-1) among healthy subjects; type B, subtypes Af-2 and MY, among the Afro-Brazilians; and type B, subtype MY, within the Surui Indians. An unexpected result was the detection of another polyomavirus, the BKV, among Afro-descendants. The present study shows, for the first time, the occurrence of JC and BK polyomaviruses infecting humans from the Brazilian Amazon region. The results show a large genetic variability of strains circulating in the region, infecting a large group of individuals. The presence of European, Asiatic and African subtypes associated to the ethnic origin of the population samples investigated herein, highlights the idea that JCV is a fairly good marker for studying the early migration of human populations, reflecting their early and late history. Furthermore, the identification of the specific mutations associated to the virus subtypes, suggests that these mutations have occurred after the entrance of the virus in the Amazon region of Brazil.

JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region

JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215bp) and IG (610bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4(+)/TCD8(+) lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.