CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis

Abstract

The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA.

Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profiles of human joint fibroblast‐like synoviocytes

“…58 It was reported that CCR5 overexpression would increase the susceptibility to RA occurrence. 59 Besides, CCR5 is the receptor of CCL5, which function acts as a chemoattractant for blood monocytes, memory T helper cells, and eosinophils. It was reported that CCL5 induced articular cartilage degradation by activating MMP-1 and MMP-13 expression in RA FLSs.…”

“…CCRs are the members of the G-protein-coupled receptor family, and they are receptors for extensive chemokines. 59 Besides, CCR5 is the receptor of CCL5, which function acts as a chemoattractant for blood monocytes, memory T helper cells, and eosinophils. 58 It was reported that CCR5 overexpression would increase the susceptibility to RA occurrence.…”

HLA and disease: guilt by association

“…Other early studies also suggested that determining SE status may be helpful more generally in selecting treatment options (O'Dell et al ., ). Other immune polymorphisms, such as CCR5 promoter SNPs, may also predispose to severe erosive disease (Han et al ., ).…”

Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis

“…The Sharp scoring method is the most widely used measure of joint damage in clinical trials and longitudinal observational studies. Several candidate gene association studies have shown genetic contributions to radiologic joint damage in RA [Han et al, 2012;Nam et al, 2010;Teare et al, 2013]. Recently, Knevel et al [2012] reported significant heritability (ß58%) of the rate of joint destruction in an Icelandic study.…”