Asunto(s)
Artritis Reumatoide , Proteínas de Transporte de Catión/genética , Zinc , Adulto , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Brasil , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Polimorfismo de Nucleótido Simple , Factores Protectores , Zinc/metabolismo , Zinc/farmacologíaRESUMEN
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder presenting heterogeneous clinical manifestations. A number of genes involved in SLE susceptibility are related to the type I interferon (IFN) pathway. IFN mediates innate immune responses and its increased levels contribute to the breakdown of peripheral tolerance. Interferon-induced helicase C domain 1 (IFIH1) activates and modulates IFN responses through its caspase recruitment domain. In this study, we analyzed four IFIH1 single nucleotide polymorphisms (SNPs): rs6432714, rs10930046, rs1990760, and rs3747517, in 337 patients with SLE and 373 healthy individuals from southeast and northeast Brazil. Our results did not find an association between IFIH1 SNPs and SLE (P value >0.025 after Bonferroni's adjustment). However, meta-analysis of peer-reviewed articles from 2008 to 2015 and data from this study indicated an association between rs1990760 and SLE onset (P < 0.05). This is the first association analysis on IFIH1 polymorphisms and SLE susceptibility in Brazilian populations.
Asunto(s)
Estudios de Asociación Genética , Interferón Tipo I/genética , Helicasa Inducida por Interferón IFIH1/genética , Lupus Eritematoso Sistémico/genética , Brasil , Predisposición Genética a la Enfermedad , Humanos , Inmunidad Innata/genética , Lupus Eritematoso Sistémico/patología , Polimorfismo de Nucleótido Simple , Transducción de SeñalRESUMEN
The aim of this study was to perform an association study between seven Fyn-binding protein gene (FYB)-tag single nucleotide polymorphisms (SNPs) and type I diabetes mellitus (T1DM), as well as with disease age of onset. We also assessed the role of FYB SNPs in the insurgence of autoimmune polyglandular syndrome type III (APSIII), characterized by the simultaneous presence of autoimmune thyroid disease and celiac disease, in patients with T1DM from a Northeastern Brazilian population. One hundred and seventy-seven patients with T1DM and 190 healthy individuals were genotyped for seven tag SNPs, covering most of the FYB locus, using real-time polymerase chain reaction amplification. There was no significant difference in the distribution of allele and genotype frequencies among patients and healthy individuals. Moreover, none of the tag SNPs were associated either to T1DM age of onset or to the insurgence of APSIII. However, since the FYB protein is a key component in T cell response, its gene variants might play a role in protein function, which might be testable in a population with different genetic backgrounds or by using functional assays.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/genética , Predisposición Genética a la Enfermedad , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , MasculinoRESUMEN
This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5' upstream regulatory region (URR), 3' untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12% in SLE patients vs 6% in controls; odds ratio (OR), 2.10, 95% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8% in SLE patients and 6.3% in controls; OR, 2.14, 95% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is far from being elucidated yet, our association study results along with a systematic review and meta-analysis suggest that HLA-G might be able to slightly modulate the complex SLE phenotype (pooled OR, 1.14, 95% CI, 1.02-1.27, P = 0.021).
Asunto(s)
Antígenos HLA-G/genética , Lupus Eritematoso Sistémico/genética , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Adulto , Alelos , Autoanticuerpos/sangre , Brasil , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígenos HLA-G/fisiología , Haplotipos/genética , Humanos , Mutación INDEL , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Evaluación de SíntomasRESUMEN
We analyzed the possible association between human leukocyte antigen-G (HLA-G) genetic variants, supposed to regulate HLA-G expression, and the susceptibility to develop rheumatoid arthritis (RA) as well as its clinical manifestations. The 5'upstream regulatory region (5'URR) and 3'untranslated region (3'UTR) regions of the HLA-G gene were screened in 127 RA patients and 128 controls: 10 5'URR and 3 3'UTR HLA-G polymorphisms as well as two haplotypes were associated with risk for RA development, while a polymorphism in the 5'URR showed an association with the degree of disease activity. These findings, although the number of cases analyzed is limited and the P-values are modest, indicate a possible association between HLA-G gene polymorphisms and susceptibility to develop RA disease and its severity.