Rheumatoid Arthritis In Egyptian Population Research Articles

Association of autoimmune regulator gene polymorphism with susceptibility to rheumatoid arthritis in Egyptian population.

The autoimmune regulator (AIRE) gene controls autoimmunity via its transcript AIRE protein that suppresses naïve T cells during central selection. The role of AIRE polymorphism in rheumatoid arthritis (RA) autoimmunity remains elusive. This study aimed to investigate the association of two selected SNPs, namely, rs760426 and rs2075876, with RA susceptibility in the Suez Canal Zone population. The study population included 100 RA patients, and the control group included 100 healthy subjects who were age- and sex-matched to the RA group. SNP genotyping was performed using real-time polymerase chain reaction-based allelic discrimination assay, the odds ratio was defined to assess the strength of the association. For rs760426, combining genotypes data revealed a significant increase for A/G genotype in the RA cases (47%, n= 47) than in the control group (27%, n= 27) in both co-dominant and over-dominant models (P= 0.013 and 0.003 respectively). In addition, rs760426 correlated to duration of RA (P= 0.031) and anti-cyclic citrullinated peptide antibody (P= 0.021). For rs2075876, there was a significant increase in the A/A genotype in RA patients compared with control subjects. In the co-dominant model, the frequency of A/A was 14% and 7% respectively (P= 0.02). In contrast to rs760426, rs2075876 associated with the risk of increased body mass index (P= 0.014) and the positivity of rheumatoid factor (RF) (P= 0.043). The frequency of minor alleles, G allele in rs760426 SNP, and A allele in rs2075876 was higher in RA patients than in control. The haplotype frequency of both G and A alleles in rs760426 and rs2075876 receptively was 11% in RA group with statistically significant difference (P= <0.001) between RA patients and healthy control. SNPs rs760426 and rs2075876 in the AIRE gene may contribute to the risk for RA susceptibility. These two polymorphisms were associated with variable risk factors and predictive biomarkers for RA. The mutant allele (G) of rs760426 SNP has significant indication of poor prognosis.

Research Article Interleukin-27-924A/G gene polymorphism is associated with Rheumatoid Arthritis in Egyptian population

Rheumatoid arthritis (RA) is an autoimmune disease with increasing activity of T lymphocytes and abnormal production of inflammatory cytokines. Interleukin-27 (IL-27), a multifunction cytokine with contradictory inflammatory effect. Polymorphism of IL-27 was reported to be predisposed to many inflammatory diseases and autoimmune diseases. We aimed to assess the role of IL-27 polymorphism in the predisposition of RA in Egyptian population. A case control study included 100 patients with RA and 100 healthy subjects represented the control group. The IL-27−924A/G gene polymorphism was investigated by RFLP-PCR. The serum level of IL-27was estimated by enzyme-linked immunosorbent assay. The AA genotype was significantly higher in patients with rheumatoid arthritis as compared with the control group (P=0.02, OR (95% CI)=0.4 (0.1-1.2). In addition, we observed significant elevation in the level of serum IL-27 in the patients group in comparison with the healthy subjects. We found that patients with AA genotype or A allele had significant higher level of serum IL-27. There was positive relationship between the serum level of IL-27 and severity of the disease. It was concluded that AA genotype of IL-27 gene might be a risk factor for the incidence of RA in Egyptian population. Patient with significantly higher blood levels of IL-27 were at risk for increasing disease activity.

Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population

Background/Aims: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the population worldwide. The aim of the present study was to investigate whether miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 polymorphisms are associated with susceptibility to RA in Egyptians and whether they influence disease severity and activity. Methods: The study was performed on 104 unrelated RA patients and 112 healthy subjects. RA patients were further subdivided into active and inactive RA groups. Polymorphisms were genotyped by using real-time polymerase chain reaction with TaqMan allelic discrimination assay. Results: Significant differences in the frequency of miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 alleles and genotypes were observed between RA patients and controls. Only CA and AA genotypes of IRAK1 rs3027898 shows a significant difference between active and inactive subgroups. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one. CG and GG genotypes of miRNA-146a rs2910164 were associated with positive erosions. CA genotype of IRAK1 rs3027898 was associated with low disease activity and negative erosions, while, the AA genotype was associated with high disease activity. CC genotype of PADI4 rs1748033 was associated with negative rheumatoid factor. Conclusion: The 4 studied SNPs were likely to play an important role in the susceptibility to RA and can influence disease severity and activity in Egyptian population.

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects (P=0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.

Genetic influence of DNAM-1 (DNAX accessory molecule-1) gene polymorphism (rs 763361) on susceptibility and disease activity of systemic lupus erythematosus and rheumatoid arthritis in Egyptian patients

Genome-wide association studies have led to the involvement of multiple susceptibility genes in the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The present case control study was conducted to determine the possible association of DNAM-1(C/T, rs 763361) single nucleotide polymorphism (SNP) with RA and SLE in the Egyptian population. This study aimed to determine the possible genetic influence of SNP on disease activity in SLE (represented by SLEDAI score) and in RA patients (represented by DAS28). Fifty SLE patients compared to 43 healthy controls and 35 RA patients compared to 30 healthy controls were included in the study. The PCR-RFLP technique was used to detect DNAM-1(C/T rs 763361) gene polymorphism. Analysis of the frequency distribution of both allele and genotype frequency distribution of SLE and RA patients compared to healthy control subjects did not reveal a significant association between SLE and RA patients and the rs763361. Analysis of the disease activity status in lupus nephritis (LN) and non-lupus nephritis patients revealed a significant association between DNAM-1(C/T) SNP and LN patients carrying the TT and CT genotypes (P = 0.009 and 0.004; respectively). DNAM-1(C/T rs763361) SNP is not associated with the development of SLE and RA in Egyptian population. The SNP might be associated with disease activity status represented by SLEDAI score in LN patients carrying CC and CT genotypes, respectively.

NRAMPI (SLC11A1) Gene-1703 G/A Polymorphisms as Prognostic and Diagnostic Marker of Rheumatoid Arthritis in Egyptian Population

Rheumatoid arthritis (RA) is an autoimmune disease with difficulty to diagnose. The association of natural resistance-associated macrophage protein-1 (NRAMP-1) gene polymorphisms with rheumatoid arthritis (RA) is the aim of this study. Methods: Two hundred individuals who were divided into two groups: RA patients group (100 Patients with RA) and control group: (100 apparently healthy subjects). NRAMP1 polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method, including D543N. Results: Rheumatoid arthritis patients demonstrated significant increase in C-reactive protein (CRP), Rheumatoid Factor Ab, Human cartilage oligomeric matrix protein (COMP) and Anti-Cyclic Citrullinated Peptide (anti-CCP) in comparison to normal. Clinical disease activity index (CDAI) and the radiological erosion score of joints in RA patients were 29.8 ± 5.3 and 60.03 ± 38.71 respectively. The G/G, G/A and A/A genotypes were 64, 33, and 3% respectively in RA patients and were 60, 25, and 15% respectively in controls with a significant difference between RA patients and controls. The CDAI and radiological erosion score of joints had the least values in NN followed by DN while DD patients had the highest levels. The patients with phenotype DD had a grade III of disease in 40 patients and grade IV in 21 patients while grade II found in three patients. However, in patients with phenotype DN, the grading of disease II, III and IV were found to be 10, 20 and 3 respectively. All patients with NN phenotype showed a grade II of disease. There was a significant difference in percentage between RA patients and controls as regard to G or A alleles distribution. The nodule associated with G/G genotype in 58.8% while bone erosion associated with G/G genotype in 65% of RA patients. Conclusion: The present study showed that NRAMP1 1703G (543D) is a risk factor for the development of RA. The estimated NRAMP1 1703G haplotype is associated with susceptibility to RA. In RA patients with 1703A, development of rheumatoid nodule is absent.

Cytotoxic T-lymphocyte-associated protein 4 gene polymorphism is related to rheumatoid arthritis in Egyptian population

Context: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a CD28-family receptor expressed on T-cells which suppresses T cell proliferation. CTLA-4 -318C/T polymorphism is involved in regulation of CTLA-4 expression.Objective: The study aimed to investigate the genetic association of CTLA-4 -318C/T polymorphism with rheumatoid arthritis (RA) and the activity and severity of the disease in the Egyptian population.Methods: A single nucleotide polymorphism (rs5742909) in CTLA-4 was genotyped in 100 RA patients and 100 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Diagnostic tests were measured for RA patients.Results: The frequency of T allele in RA patients was significantly higher than in the control subjects (p = 0.002). CT and TT genotypes had high C-reactive protein, erythrocyte sedimentation rate and disease activity score 28 while CC genotype had a high rheumatoid factor.Conclusion: A minor allele of CTLA-4 rs5742909 polymorphism was associated with RA and the activity but not the severity of the disease.

Assessment of the -174G/C (rs1800795) and -572G/C (rs1800796) Interleukin 6 Gene Polymorphisms in Egyptian Patients with Rheumatoid Arthritis.

AIM:This study aimed to investigate genotype and allele frequencies of −174 (rs1800795) and −572 (rs1800796) IL-6 promoter gene polymorphisms in Egyptian patients with rheumatoid arthritis (RA) in comparison to control group.METHODS:The study was conducted on 198 Egyptian subjects (99 RA patients and 99 healthy control). The promoter region of the IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes.RESULTS:No statistical differences were found in −572G/C genotype (P = 0.177) or allele (P = 0.147) frequencies between RA patients and controls. Significant differences were observed in −174G/C genotype (P < 0.001) and allele (P < 0.001) frequencies between RA patients and controls.CONCLUSION:A significant association of IL-6 −174G/C gene polymorphism and RA in Egyptian population was found with significantly higher frequencies of GC and CC genotypes and C allele in RA patients compared to controls. No association was found between IL-6 −572G/C gene polymorphism and RA.

Association of the polymorphisms of TRAF1 (rs10818488) and TNFAIP3 (rs2230926) with rheumatoid arthritis and systemic lupus erythematosus and their relationship to disease activity among Egyptian patients.

Aim of the studyRecent studies demonstrated the association of tumor necrosis factor α-induced protein 3 (TNFAIP3) (rs2230926) and tumor necrosis factor receptor associated factor 1 (TRAF1) (rs10818488) with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in different populations. We aimed at determining whether they confer susceptibility to SLE and RA in Egyptian population and if there is any relation to disease activity and auto-antibodies profile.Material and methodsA case-control study involving 105 individuals with RA, 90 with SLE and 75 healthy controls was performed using TaqMan genotyping assay for two SNPs that showed the best evidence of association in the previous Caucasian studies.ResultsWe detected significant differences in G allele frequency of TNFAIP3 (rs2230926) with SLE (p = 0.017*) and RA (OR = 2.333; 95% CI: 1.103-4.935, p = 0.023*) and association with RA disease activity (< 0.001). The A allele of TRAF1 was significantly increased in RA compared to controls(p = 0.049) and with RA activity (p = 0.001), while TRAF1 polymorphism did not exhibit any significant difference in the frequencies of genotypes or alleles in SLE and control (p = 0.280).ConclusionsTNFAIP3 is a susceptibility gene to SLE and RA in the Egyptian population and is correlated to disease activity and the presence of autoantibodies while TRAF1 polymorphisms increase the risk of RA but not to SLE in Egyptian populations.

Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibility and severity of rheumatoid arthritis in Egyptian population

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which interleukin-4 (IL-4) plays an important role. This study aimed to investigate the influence of IL-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms on RA susceptibility, activity and severity in Egyptian population. Materials and methodsOne hundred and seventy-two RA patients and 172 controls were enrolled in this study. IL-4 VNTR and IL-4-590 promoter polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IL-4 and anti-cyclic citrullinated peptides (anti-CCPs) antibody concentrations were measured by enzyme linked immunosorbent assay (ELISA). ResultsSubjects with IL-4-590 TT genotype were significantly more likely to develop RA. IL-4 VNTR 1/1 genotype, IL-4-590 TT and CT genotypes were significantly more associated with erosive RA and positive anti-CCP antibody. RA severity parameters were significantly increased, while, IL-4 level was significantly decreased in RA patients with IL-4 VNTR 1/1 and IL-4-590 TT genotypes. Only patients with IL-4-590 TT genotype showed a significant increase of all RA activity parameters. ConclusionIL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA.

Influence of TRAF1/C5 and STAT4 genes polymorphisms on susceptibility and severity of rheumatoid arthritis in Egyptian population

Rheumatoid arthritis (RA) is the most common cause of adult inflammatory arthritis. Recent genome-wide association scans have disclosed several single-nucleotide polymorphisms associated with RA susceptibility. The aim of this study was to determine whether the polymorphisms of TRAF1/C5 (tumor necrosis factor (TNF)-receptor associated factor 1)/(complement component 5) and STAT4 (signal transducers and activators of transcription 4) confer susceptibility, activity and severity to RA in Egyptian populations. One hundred and seventy-two RA patients and 160 controls were enrolled in the study. Polymorphisms of TRAF1/C5 and STAT4 genes were determined using restriction fragment length polymorphism–polymerase chain reaction. The TRAF1/C5 A and STAT4 T alleles were significantly associated with RA in Egyptian population. TRAF1/C5 A allele and STAT4 TT genotype were significantly associated with RA severity. In conclusion the mutant alleles or genotypes of both examined polymorphisms are associated with the development of RA in Egyptian population.