Expression of vitamin D-binding protein in synovial tissues of rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective To screen the proteins with decreased expression in the synovial tissues of rheumatoid arthritis (RA) patients by comparing their expression profiles with that of osteoarthritis (OA) and ankylosing spondylitis (AS) patients by a proteomic approach,and to explore the association of reduced expression with disease susceptibility by a single nucleotide polymorphism (SNP) analysis.Methods Proteins extracted from the synovial membranes (n=10 for each disease) were separated by 2-D electrophoresis.The proteins with significantly decreased expression in the RA samples were subjected to MALDI-TOF-MS.The results were verified using Western blotting.Tag SNPs located in the targeted gene were assessed using the Taqman assay in a cohort of 267 Chinese patients with RA and 160 healthy controls.The genotyping results were confirmed in a large cohort of 389 patients with RA and 371 healthy controls.SPSS 11.5 software package was used for one way ANOVA and Fisher's exact test.Results The expression of vitamin D-binding protein (VDBP) in the synovial membranes from patients with RA was significantly decreased when examined by proteomic approach.This result was confirmed by Western blotting analysis.The rs2282679 was significantly associated with RA (P=0.026 794).This result was confirmed in a large cohort of RA( OR=0.678 639,95％CI 0.54l 113-0.851 118,P=0.000 776).Conclusion Compared with samples from patients with OA and AS,RA patients' synovial tissues have low VDBP expression when examined by the proteomic method.The tag SNP rs2282679 located in VDBP is significantly associated with RA.The decreased expression and the genetic effect of VDBP in RA suggest that a novel pathogenic pathway,in which vitamin D contributes,may be involved in the arthritis process of RA.