Polymorphisms of COTL1 gene identified by proteomic approach and their association with autoimmune disorders

• Published in: Experimental & molecular medicine Vol. 41; no. 5; pp. 354 - 361
• Main Authors: Jin, Eun-Heui, Shim, Seung-Cheol, Kim, Hwan-Gyu, Chae, Soo-Cheon, Chung, Hun-Taeg
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2009; Springer Nature B.V; Korean Society of Medical Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Electrophoresis, Gel, Two-Dimensional; Genotype; Humans; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Medical Biochemistry; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Molecular Medicine; Original; Polymorphism, Genetic - genetics; Proteome - genetics; Proteomics - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stem Cells; 생화학; electrophoresis, gel, two-dimensional; systemic lupus erythematosus; proteomics; rheumatoid arthritis; COTL1 protein, human; polymorphism, single nucleotide
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.3858/emm.2009.41.5.040

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.