RESUMO
Large genome-wide analysis studies (GWAS) and meta-analyses have dramatically increased our knowledge of the genetic risk factors of inflammatory bowel disease (IBD), identifying at least 163 loci. The endoplasmic reticulum aminopeptidase-2 ( ERAP2) gene has been reported as a potential candidate gene for IBD. GWAS have also shown the potential associations between ERAP single nucleotide polymorphisms (SNP) loci and susceptibility to several autoimmune diseases, and ERAP1 and ERAP2 polymorphisms are related to HLA class I-associated diseases, including ankylosing spondylitis and Behçet's disease. Interestingly, these associations were confined to individuals carrying HLA class I-risk alleles. The aim of this study was to investigate the association of ERAP1 and ERAP2 SNPs with IBD in a Spanish population, analysing their possible interaction with specific HLA-C alleles to IBD susceptibility. A total of 367 individuals were divided into 216 IBD cases and 151 controls. SNP genotyping was performed using TaqMan® genotyping assays, whereas HLA-C typing was analysed by sequence-specific oligonucleotide probing. Herein, we report an association of the ERAP1 SNP rs30187 with the HLA-C*07 allele. The existence of shared inflammatory pathways in immunologically related diseases together with the understanding of ERAP1 function may offer clues to novel treatment strategies.
Assuntos
Aminopeptidases/genética , Genótipo , Antígenos HLA-C/genética , Doenças Inflamatórias Intestinais/genética , Antígenos de Histocompatibilidade Menor/genética , Apresentação de Antígeno , Citotoxicidade Imunológica , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Modelos Imunológicos , Mimetismo Molecular , Polimorfismo de Nucleotídeo Único , Risco , EspanhaRESUMO
La artritis reumatoide (AR) es una enfermedad sistémica crónica y autoinmune, que afecta principalmente a las articulaciones sinoviales. Al igual que ocurre con muchas enfermedades autoinmunes, la etiología de la AR es multifactorial y desconocida. La susceptibilidad genética es evidente en AR, situando su heredabilidad en aproxima-damente el 60%. La importancia del conocimiento de los factores genéticos asociados con la AR se sitúa en la contribución a la comprensión de los mecanismos patogénicos de la enfermedad, así como a su aplicación clínica que nos acerque a un tratamiento más personalizado de los pacientes por medio de marcadores de riesgo, diagnóstico y/o pronóstico. En este artículo se revisan los factores genéticos de la AR, y se hace una aproximación a la situación en poblaciones latinoamericanas en general, y chile-na en particular.
Rheumatoid arthritis (RA) is an autoimmune inflammatory rheumatic disease that affects many tissues and organs, mainly synovial joints. Like many autoimmune dis-eases, the etiology of RA is multifactorial and unknown. Genetic susceptibility is evi-dent in RA, with its heritability around the 60%.The relevance of the knowledge of the genetic factors associated with RA relies on its contribution to the understanding of the pathological mechanisms of the disease, and the clinical applicability. This better understanding let us develop a more personalized treatment through genetic markers for risk, diagnostic and prognostic. In this paper, genetic factors of RA are reviewed and a general view of the Latin American populations, and particularly Chilean, is made.
Assuntos
Humanos , Artrite Reumatoide/genética , Predisposição Genética para Doença , Doenças Autoimunes , Variação Genética , Etnicidade , Chile/epidemiologia , Estudos de Associação GenéticaRESUMO
We aimed to analyze the possible association of KIR/HLA-C genotypes with the susceptibility to Crohn's disease (CD) in a Spanish population. A total of 125 patients with CD and 339 healthy controls were selected for this study. KIR and HLA-C typing were developed by sequence-specific oligonucleotide probing. We found that the centromeric A/A genotype and HLA-C1 combination was significantly increased in CD patients (P<10(-3)). The KIR2DL3/2DL3 genotype was significantly increased in CD patients (P<0.0005). Moreover, we also observed a highly significant increase of KIR2DL3-HLA-C1 homozygosis in CD patients (P<0.0005). Our results confirm the relevance of the KIR2DL2/KIR2DL3 genes and their interaction with HLA-C to CD. We show that the contribution of the KIR genes to CD susceptibility extends beyond the association with individual KIRs, with an imbalance between activating and inhibitory KIR genes seeming to influence the susceptibility to CD.