title: 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.
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Luterek-Puszyńska
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland.|Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Damian
authors.initials: D
authors.lastname: Malinowski
authors.affiliation: Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Paradowska-Gorycka
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland. pawand@poczta.onet.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlik
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004247:DNA
keywords: CCL5; CD28; CTLA-4; Polymorphism; Rheumatoid arthritis