ABSTRACT
Increasing evidence suggests that the rs6822844, within KIAA1109/TENR/IL2/IL21 gene cluster on 4q27, is strongly associated with rheumatoid arthritis (RA) in the Caucasian population. The aim of this study is to investigate the possible association between the SNP rs6822844 and susceptibility to RA in the Algerian Maghreb population, and to explore the association with the clinical and immunological features of RA. The polymorphism rs6822844 was genotyped in 323 RA patients and 323 healthy individuals using the TaqMan assay. A strong association of IL2/IL21 with RA susceptibility was detected in the Algerian population [odds ratio (OR) = 2.57 (95% confidence interval (CI) 1.74-3.83), P = 10(-4) ]. Our results revealed that IL2/IL21 predisposed to disease development in both autoantibody positive and negative disease. Meanwhile, the association was stronger in RA patients with anti-cyclic citrullinated peptides (ACPA) positive than those with ACPA negative [OR = 2.30 (95% CI 1.53-3.51), P = 10(-4) and OR = 1.98 (95% CI 1.01-4.22), P = 0.037, respectively]. Moreover, our findings showed a moderate association of the rs6822844 polymorphism with disease activity (P = 0.014). This study indicates for the first time that there is a strong association between IL2/IL21 rs6822844 variant and susceptibility to RA in the Algerian population, and that this association was independent from the autoantibodies status of RA patients.
Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Loci , Genetic Predisposition to Disease , Guanine Nucleotide Exchange Factors/genetics , Interleukin-2/genetics , Interleukins/genetics , Polymorphism, Single Nucleotide , Adult , Algeria , Arthritis, Rheumatoid/ethnology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Autoantibodies/biosynthesis , Autoantibodies/genetics , Case-Control Studies , Chromosomes, Human, Pair 4/chemistry , Ethnicity , Female , Gene Expression , Genetic Association Studies , Guanine Nucleotide Exchange Factors/immunology , Humans , Interleukin-2/immunology , Interleukins/immunology , Male , Middle Aged , Severity of Illness Index , White PeopleABSTRACT
OBJECTIVES: One of the most important pro-inflammatory cytokines in the pathophysiology of rheumatoid arthritis (RA) is interleukin 1 (IL-1). The purpose of this study is to evaluate the association between IL-1B (-511), IL-1 (+3953), IL-1 RN variable number of tandem repeat (VNTR) polymorphisms and the occurrence in Algerian patients with rheumatoid arthritis. We also analyze their correlations with clinical and biological phenotypes. PATIENTS AND METHODS: One hundred and forty-seven patients with RA (119 women, 28 men) and 127 controls (70 women, 57 men) were included in the study. The analysis of two polymorphisms of IL-1B-511 and IL-1B+3953 was done by PCR-RFLP. Analysis of IL1-RN VNTR polymorphism was performed by PCR. RESULTS: No significant difference in genotype, allelic and haplotype distribution at the three polymorphisms was observed between RA patients and controls. However, the genotype (T/T) polymorphism of IL-1B-511 is more frequent in the group of patients with positive ACPA compared with negative ACPA group (Pc=0.01, OR=4.65). Moreover, we noted that the haplotype (IL-1RN* 1/IL-1B-511T/IL-1B+3953C) was more frequent (Pc=0.03, OR=2.05) in the positive ACPA group. CONCLUSION: The association between the allele 1 of IL-1 RN VNTR, T allele of IL1B-511 and C allele of IL1-B +3953 polymorphisms seems to predispose to the synthesis of ACPA and therefore to the occurrence of ACPA positive RA. Further studies with a larger number of patients are needed to define the real role of IL-1 in the susceptibility to or severity of RA.
