RESUMEN
Genome-wide association studies (GWAS) have identified hundreds of new potential genetic risk loci associated with numerous complex diseases such as multiple sclerosis (MS). Genes which have been discovered by GWAS are now the focus of numerous ongoing studies. The goal of this study was to confirm and understand the potential role of one of such genes-transmembrane protein 39A gene (TMEM39A)-in multiple sclerosis.We showed the difference in TMEM39A messenger RNA (mRNA) expression between MS patients and controls (T 22;74 = 5.429; p = 0.0063). In our study, the lower mRNA expression of TMEM39A gene in patients did not correlate with a higher methylation level of the TMEM39A promoter. Moreover, a decreased level of TMEM39A mRNA was associated neither with rs1132200 nor with rs17281647. Additionally, we did not find an association between these two TMEM39A polymorphisms and the risk and progression of multiple sclerosis.Our investigation is the first which indicates that TMEM39A mRNA expression may be associated with the development and/or course of multiple sclerosis.
Asunto(s)
Metilación de ADN , Proteínas de la Membrana/genética , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple , Femenino , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Esclerosis Múltiple/patología , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
CD28/CTLA-4CD80/CD86 molecules play an important role in the regulation of T cells activation. Defects in proteins involved in this pathway may lead to the development of autoimmune diseases in which T cells are involved. In this casecontrol study (336 multiple sclerosis (MS) patients and 322 controls) we investigated the possible association of eleven polymorphisms in CD28, CTLA-4, CD80 and CD86 genes with susceptibility to MS and/or its progression. We also took into account HLA-DRB1*15:01 status. Moreover, this study aimed to determine the possible gene-gene interactions between examined SNPs associated with the susceptibility to MS and its outcome. Our investigation revealed that in HLA-DRB1*15:01 negative individuals, G allele in rs231775A NGof CTLA-4 gene was associatedwith higher risk ofmultiple sclerosis. Additionally, the association of rs2715267T NGof CD86 gene withMS susceptibilitywas detected. In details, carriers of G allele at this polymorphic site possessed higher risk of MS in comparison to TT homozygotes. On the other hand, the lower risk of MS was observed in individuals carrying A allele at the rs1599795T N A polymorphic site of CD80. Furthermore, the analysis revealed an interaction between three polymorphisms: rs3116496T N C (CD28), rs6641T N G (CD80) and rs17281995G N C (CD86), associated with the age of MS onset.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Esclerosis Múltiple/genética , Adulto , Edad de Inicio , Antígeno B7-1/genética , Antígeno B7-2/genética , Antígenos CD28/genética , Antígeno CTLA-4/genética , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
CD40-CD40L interactions mediate T-dependent B cell response and efficient T cell priming. Therefore, genes encoding these molecules are attractive candidates for studies on autoimmune diseases, such as multiple sclerosis (MS), in which activated T and B cells are involved. Thus, we analyzed CD40 and CD40L mRNA expression in whole blood samples from MS patients and controls. Additionally, we examined the effect of three SNPs of CD40 (rs1883832C>T, rs11569343C>G, and rs752118C>T) and two SNPs of CD40L (rs3092923T>C and rs3092952A>G) on their mRNA expression. Our results showed that the rs1883832C>T SNP affects CD40 gene expression. Our analysis revealed that individuals possessing CT and TT genotypes (predisposing to MS) had decreased level of CD40 mRNA in comparison to those with CC. Moreover, we demonstrated the potential role of impaired CD40-CD40L interaction in developing of multiple sclerosis.
Asunto(s)
Alelos , Antígenos CD40/genética , Esclerosis Múltiple Recurrente-Remitente/genética , Polimorfismo de Nucleótido Simple , ARN Mensajero/metabolismo , Estudios de Casos y Controles , Regulación hacia Abajo , Femenino , Humanos , Masculino , ARN Mensajero/genéticaRESUMEN
The authors presented the clinical and anatomopathological description of Arnold-Chiari anomaly at 25 years old man, which caused cerebellar manifestation and sudden death. At the base of anatomopathological study the first type of Arnold-Chiari anomaly with dislocation of cerebellum tonsils into foramen magnum was recognized.