Single nucleotide polymorphisms in the interferon gamma gene are associated with distinct types of retinochoroidal scar lesions presumably caused by Toxoplasma gondii infection

The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ gene ( IFNG ) with different types of retinal scar lesions presumably caused by toxoplasmosis were investigated in a cross-sectional population-based genetic study. Ten SNPs were investigated and after Bonferroni correction, only the associations between SNPs rs2069718 and rs3181035 with retinal/retinochoroidal scar lesions type A (most severe scar lesions) and C (least severe scar lesions), respectively, remained significant. The associations of two different IFNG SNPs with two different types of retinal lesions attributable to toxoplasmosis support the hypothesis that different inflammatory mechanisms underlie the development of these lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear cells stimulated with Toxoplasma gondii antigens was also investigated. The association between SNP rs2069718 and type A scar lesions revealed that differential IFN-γ levels are correlated with distinct genotypes. However, no correlation was observed with IFN-γ secretion levels and the SNP rs3181035 , which was significantly associated with type C scar lesions. Our findings strongly suggest that immunogenetic studies of individuals with congenital or postnatally acquired infection are needed to better understand the role of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis.

CTLA4 CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus

Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4 CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed.

Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians

The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3 percent), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2 percent). This allele is uncommon in Afro-Brazilians (2.0 percent), rare in the Guarani Amerindians (0.4 percent) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7 percent) and R60S in the Afro-Brazilians (5.0 percent). A29S and L55Q present an impaired response to beta-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4 percent and 2.7 percent, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4 percent) and Y68C (g.2964A > G) in Kaingang (10.3 percent). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations.

Absence of the -116A variant of the butyrylcholinesterase BCHE gene in Guarani Amerindians from Mato Grosso do Sul

Butyrylcholinesterase (BChE; EC 3.1.1.8; Online Mendelian Inheritance in Man (OMIM) number 177400) is an enzyme found in many human tissues and encoded by the BCHE gene, of which 65 variants have been identified. In a recent study we found that the -116A variant of exon 1 of the BCHE gene was associated with lower mean BChE activity. The present study analyzed the -116 single nucleotide polymorphism (SNP) in 253 Guarani Amerindian Brazilians from the state of Mato Grosso do Sul (148 Guarani-Kaiowá, 83 Guarani-Ñandeva and 22 Kaiowá-Ñandeva descendants) and verified that they were all homozygotic for the -116G variant. A comparative analysis of the -116 site in nine vertebrate species indicated the -116A variant as the ancestral type. This is the first study of the -116 SNP in Amerindians and it is therefore difficult to infer whether or not the -116A variant was always absent from southern paleo-Amerindians or was present and then subsequently lost due to evolutionary factors.

Programmed cell death 1 gene (PDCD1) polymorphism and pemphigus foliaceus (fogo selvagem) disease susceptibility

Pemphigus foliaceus, also known as fogo selvagem, is an autoimmune disease of the epidermis characterized by superficial blisters and antibodies against desmoglein 1. It is a multifactorial disease and genetic susceptibility is oligogenic or polygenic. Considering the crucial function of the programmed cell death 1 molecule (PD-1) in the immune response, the aim of this study was to verify if variants of the PDCD1 gene influence susceptibility and resistance to pemphigus foliaceus, in a case - control disease association study. We analyzed patients (n = 154) and unaffected control individuals (n = 325) of the Brazilian population, in respect to the PD1.3(G,A) PD1.5(C,T) and PD1.6(A,G) single nucleotide polymorphisms (SNPs) and also investigated, for the first time, the exon 5 PDCD1 microsatellite (CTG)n. The patient and control samples were divided into strata, according to the predominant ancestry of the individuals (African or European). The PD1.5 genotype distribution in the patients sample was almost indistinguishable from that in the control sample, in both population strata. A possible negative association between pemphigus foliaceus and allele PD1.3A was observed in the total African and European ancestry population sample (odds ratio (OR) = 0.55, p = 0.066) and should be investigated in forthcoming studies. The PD1.6A allele was over-represented among the patients of predominantly European ancestry due to an increase of both the G/A and the A/A genotypes (OR = 2.12 and 1.74, respectively; p = 0.035). We conclude that polymorphisms of the PDCD1 gene may influence susceptibility to pemphigus foliaceus, at least in Brazilians of predominantly European ancestry.

Butyrylcholinesterase genetic variability in Guarani Amerindians from the Brazilian state of Mato Grosso do Sul

Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a polymorphic enzyme coded by the BCHE gene (3q26.1-q26.2) while the CHE2 gene (2q33-q35) determines a still not characterized substance that forms a complex with BChE (C5), being the CHE2 C5+ and CHE2 C5- phenotypes detected in electrophoresis. The present study investigated BCHE and CHE2 variability and the BChE activity of Brazilian Guarani Amerindians from the Kaiowá and Ñandeva sub-groups living in several indigenous territories in the Brazilian state of Mato Grosso do Sul. The frequency of the BCHE exon 2 D70G (A) allele was 0.60 percent ± 0.35 percent while that of the BCHE exon 2 G390V (F-2) allele, never before screened in Amerindians, was 8.82 percent ± 1.35 percent. This is the first time that the BCHE gene exon 4 A539T (K) allele has been surveyed in Brazilian Amerindians where it was found at a frequency of 3.69 percent ± 0.85 percent, similar to that found in Chilean Mapuche Amerindians. The BCHE gene variability seen in this survey differs from that of non-isolated populations in respect to both A539T and G390V allele frequency. The CHE2 C5+ phenotype frequency was 14.40 percent ± 2.22 percent and falls within the range of that found for other Brazilian Amerindian samples.

Human T - cell lymphotropic virus type II in Guaraní Indians, Southern Brazil

O vírus linfotrópico de células T-humanas do tipo II (HTLV-II) é identificado em muitos grupos de ameríndios. No Brasil, tem sido encontrado em indivíduos da população urbana, bem como em índios oriundos da região Amazônica. Os Índios Guaraní, do Sul do país, foram investigados para infecção por HTLV-I/II. Três indivíduos, oriundos de uma amostra de 52 índios, demonstraram sororeatividade para HTLV-II (ensaio imunoenzimático e Western blot). Este estudo preliminar foi o primeiro a identificar a presença de infecção por HTLV-II em ameríndios do Sul do Brasil.

Perfil de auto-anticorpos em indios das tribos Kaingang e Guarani do Sul do Brasil / Autoantibody profile among Kaingang and Guarani Indians in southern Brazil

O presente estudo teve por objetivo investigar o perfil de auto-anticorpos em 241 amostras de sangue de 176 indios Kaingang 6 65 indios Guarani de tres populacoes das reservas indigenas do Rio das Cobras e Ivai, no Estado do Parana, regiao Sul do Brasil. Foram investigados os anticorpos antimusculo liso, antimitocondrias, antinucleares, anticelulas gastricas parietais e antimicrossomas de figado e rim, por metodo de imunofluorescencia indireta. Os resultados foram comparados com os de um grupo de 100 individuos sadios, pertencentes a populacao geral. Obteve-se uma positividade total de 9 por cento para a populacao indigena investigada e 4 por cento para os controles, com resultado significativo para prevalencia dos anticorpos antimusculo liso nas populacoes Kaingang e Guarani do Rio das Cobras (P= 0,03). E provavel que as praticas culturais envolvendo escarificacoes, tatuagens e processamento oral de alimentos, aliadas ao processo de aculturacao e maior convivio com populacoes nao indigenas, exponham os indios a doencas infecciosas anteriormente inexistentes entre os mesmos. Possiveis mecanismos de mimetismo molecular a antigenos virais ou bacterianos poderiam explicar a presenca desses auto-anticorpos nessas populacoes indigenas

Lack of association between parenchymal neurocysticercosis and HLA Class I and Class II antigens

Neurocysticercosis, caused by encysted larvae of the tapeworm Taenia solium, is the most common infection of the central nervous system and a major public health problem in many countries. Prevalence in the region of Curitiba, located in the southern Brazilian State of Paraná, is one of the highest in the world. The genetics of host susceptibility to neurocysticercosis (NCC) is still obscure. To investigate if major histocompatibility complex (MHC) genes influence individual susceptibility to NCC, we performed a case-control association analysis. Fifty-two Caucasoid patients and 149 matched controls were typed for antigens of the HLA-A, B, C, DR and DQ loci. All patients had computerized tomography and clinical features compatible with parenchymal NCC. Indirect immunofluorescence of cerebrospinal fluid showed that 19 (37 per cent) of the patients presented anti-cysticercus antibodies at titers > or = 1:10. Frequencies of HLA specificities in the whole group of patients and in the subgroup with antibodies in cerebrospinal fluid were compared to those of the control group. No significant difference was found. These results do not support the hypothesis of HLA gene participation in susceptibility to parenchymal neurocysticercosis.