Fatores Genéticos Relacionados à Susceptibilidade a Doenças Auto-imunes. / Factors Related to the Genetic Susceptibility to Autoimmune Diseases.

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

21/02/2011

RESUMO

Autoimmune diseases, such as Diabetes Mellitus type 1 (DM1), celiac disease (DC) and atopic dermatitis (DA), are multifactorial disorder elicited by a complex interplay of environmental, genetic and immunologic factors. Unfortunately, remains obscure all genetic factors involved on the onset of autoimmune diseases. The aim of our study was to propose an immunegenetic model against autoimmune disorders using genes of innate immune system. Thirteen single nucleotide polymorphisms (SNPs) was selected, in the MBL2 (3), DEFB1 (3), NALP3 (2), NALP1 (2) and HLA class II (2), to analyze in patients affected with DM1 (n=214), DC (n=59) e DA (n=165). The healthy group was composed of 300 individuals without history of autoimmune disorder. Both groups came from the Recife, North East of Brazil. The SNP detection was performed through real time PCR (ABI platform) and gene sequencing (MegaBace platform). All SNPs studied were according the Hardy-Weinberg Equilibrium. The mutant allele of MBL2 gene was more frequent (p>0.05) in DM1 and DA patients than in healthy controls. The SNP G of NALP3 (rs10754558) was significantly more present (p>0.05) in patients with DM1, while the SNP A (rs35829419) of NALP3 gene was less frequent in patients than in control group. The HLA-DR3 and DR4 was strong associated with the onset of DM1 and DC. Any association was found in the frequency of the DEFB1 and NALP1 gene in all studied populations. Our results confirm the important role of MBL2 and NALP3 genes on the susceptibility of autoimmune disorders. Our autoimmune model is based in a systemic effect of MBL2, NALP3 and HLA class II in the organism. The SNPs of MBL2 and NALP3 affect the serum levels of the protein. Low levels of MBL protein and high levels of NALP3 could increase the production of IL-1 beta, and consequently, the degree of inflammatory response, where the risk HLA facility the process of autoantigens presentation. Those events were previously associated with other autoimmune diseases, thus we suggest that patients carrying mutant alleles of MBL2 and NALP3, in addition with the risk HLA posses a high risk to develop autoimmune disorders.

ASSUNTO(S)

diabetes mellitus doença celíaca dermatite atópica genetica diabetes mellitus, celiac disease, dermatitis atopic

ACESSO AO ARTIGO

Documentos Relacionados