CD28, CTLA-4 and CCL5 gene polymorphisms in patients with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction caused by infiltrating leukocytes including T cells. An important role in T cell co-stimulation is played by the CD28, as a stimulatory signal transducer and the inhibitory CTLA-4. CCL5 is produced by circulating T cells and plays an active role in the chemotactic activity of T cells in RA. The aim of this study was to examine the associations between polymorphisms within CD28, CTLA-4, and CCL5 genes and RA. We examined 422 patients (340 female, 82 male, mean age 57.5 ± 12.5 years) with rheumatoid arthritis and 338 healthy subjects (261 female, 77 male). Disease activity was determined on the basis of DAS28 score. The patients with DAS28 of ≤2.5 were classified as subjects in remission of disease symptoms; the patients who had DAS28 of >2.5 were classified as subjects with active form of RA. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. A statistically significant difference was observed in the distribution of CTLA4 exon 1 +49A>G rs231775 genotypes between patients with DAS28 ≤ 2.5 and DAS28 > 2.5 where the increased frequency of AA genotype among patients with DAS28 > 2.5 was revealed (OR 1.55; 95% CI 1.01-2.38). The results of our study suggest no significant association between CD28 rs1980422, CCL5 rs2107538, CTLA-4 exon 1 +49A>G rs231775 and rs3087243 gene polymorphisms and RA in the Polish population. Our results indicate a possible association between CTLA-4 exon 1 +49A>G rs231775 gene polymorphism and RA activity.

A sequencing study of CTLA4 in Pakistani rheumatoid arthritis cases

“…In our study, rs3087243/G was associated with an increased risk of RA, as has also been reported in Europeans and Asians [27,29]. However, in Mexicans rs3087243/G was associated with decreased RA risk [30], but it showed no association in the Polish population [31]. Two RA GWAS-implicated CTLA4 SNPs (rs11571302, a downstream variant, and rs231735, an upstream variant), which were not covered in our sequencing sample, are also in LD with rs3087243 (Fig 3) [32,33].…”

Identification of susceptibility SNPs in CTLA-4 and PTPN22 for scleritis in Han Chinese

“…It should be noted that studies in autoimmune disease showed controversial results concerning allele and genotype associations with several SNPs as well as other haplotype associations in the CTLA4 and PTPN22 genes [25,27,44,45]. This may be due to ethnic or geographical factors of the studied population.…”

Association Between CTLA-4 Gene Polymorphism and Risk of Rheumatoid Arthritis (RA): Evidence from a Meta-analysis Involving 21681 Cases and 23457 Controls.

“…Apart from the human leukocyte antigen (HLA) locus, a well-known genetic risk factor for RA, numbers of other susceptibility genes and loci have been characterized [6]. Recently, a growing body of non-HLA genetic predisposition studies have been conducted on the association with the risk of RA [7][8][9].…”

“…However, the conclusions which previous reports drew are inconsistent and incomprehensive. Although the association of CTLA-4 genetic polymorphisms and the risk of RA has been assessed in several meta-analyses [21][22][23], some recent studies also described this association in different populations in the past several years [9,15,[24][25][26][27]. Hence these studies should be included to increase statistical power and gain the reliable conclusion.…”