RESUMEN
To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.
Asunto(s)
Humanos , Artritis Reumatoide/genética , Enfermedades Autoinmunes/genética , Estudios de Casos y Controles , Electroforesis en Gel Bidimensional , Genotipo , Lupus Eritematoso Sistémico/genética , Proteínas de Microfilamentos/genética , Polimorfismo Genético/genética , Proteoma/genética , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.
Asunto(s)
Humanos , Artritis Reumatoide/genética , Enfermedades Autoinmunes/genética , Estudios de Casos y Controles , Electroforesis en Gel Bidimensional , Genotipo , Lupus Eritematoso Sistémico/genética , Proteínas de Microfilamentos/genética , Polimorfismo Genético/genética , Proteoma/genética , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Human leucine-rich alpha-2-glycoprotein 1 (LRG1 ) was first identified as a trace protein in human serum. The primary sequence of LRG1 includes repeated leucine residues and putative membrane-binding domains. But, there is no published information on the genetic variation of this gene. In this study, LRG1 was identified as one of several upregulated genes in RA patients. We examined the expression levels of LRG1 between an RA patient and a healthy control by RT-PCR and validated that LRG1 was highly expressed in RA patients compared with controls. We identified the possible variation sites and single nucleotide polymorphisms (SNPs) in the human LRG1 gene by direct sequencing and analyzed the association of genotype and allele frequencies between RA patients and a control group without RA. We further investigated the relationship between these polymorphisms and the level of RF or anti-CCP in RA patients. We identified a total of three SNPs (g.-678A> G, g.-404C>T and g.1427T>C) and two variation sites (g.-1198delA and g.-893delA) in the LRG1 gene. Our results suggest that polymorphisms of the LRG1 gene are not associated with the susceptibility of RA in the Korean population.