ABSTRACT
Objective: To present the frequency of single nucleotide polymorphisms of a few immune response genes in a population sample from São Paulo City (SP), Brazil. Methods: Data on allele frequencies of known polymorphisms of innate and acquired immunity genes were presented, the majority with proven impact on gene function. Data were gathered from a sample of healthy individuals, non-HLA identical siblings of bone marrow transplant recipients from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, obtained between 1998 and 2005. The number of samples varied for each single nucleotide polymorphism analyzed by polymerase chain reaction followed by restriction enzyme cleavage. Results: Allele and genotype distribution of 41 different gene polymorphisms, mostly cytokines, but also including other immune response genes, were presented. Conclusion: We believe that the data presented here can be of great value for case-control studies, to define which polymorphisms are present in biologically relevant frequencies and to assess targets for therapeutic intervention in polygenic diseases with a component of immune and inflammatory responses.
Objetivo: Apresentar a frequência de polimorfismo de nucleotídeo único de alguns genes da resposta imune em amostra populacional da cidade de São Paulo (SP). Métodos: Foram apresentadas as frequências de alelos de conhecidos polimorfismos de genes de imunidade inata e adquirida, a maioria com impacto funcional comprovado. Os dados foram coletados a partir de amostras de indivíduos saudáveis, irmãos não-HLA idênticos, de receptores de transplante de medula óssea do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, obtidos entre 1998 e 2005. O número de amostras variou para cada polimorfismo de nucleotídeo único analisado por reação em cadeia pela polimerase seguida de clivagem com enzimas de restrição. Resultados: Apresentou-se a distribuição de alelos e genótipos de 41 polimorfismos genéticos, a maioria de genes para citocinas, mas também incluindo outros genes de resposta imune. Conclusão: Acreditamos que os dados apresentados aqui possam ser de grande valor para definir quais os polimorfismos presentes em frequências relevantes, para estudos caso-controle e para avaliar alvos de intervenção terapêutica nas doenças poligênicas com componente de resposta imune ou inflamatória.
Subject(s)
Cytokines , Immunity, Innate , Polymorphism, GeneticABSTRACT
BACKGROUND: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). AIMS: To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our cohort, nine (47 percent) patients were homozygous for the C282Y mutation, two (11 percent) were heterozygous for the H63D mutation, and one each (5 percent) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. CONCLUSIONS: One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.