Detection of the −1082 G/A Promoter Polymorphism of Interleukin-10 Gene by ARMS-PCR Technique among some Iraqi Rheumatoid Arthritis Patients (original) (raw)
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Modern Rheumatology, 2007
In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: -1087G>A), rs1800871 (position: -824C>T) and rs1800872 (position: -597C>A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P>0.05). However, a significant difference was observed in allele frequencies of -824CT, -824TT, -597CA, and -597AA between the RA patients and healthy volunteers (P=0.04). The -1087A/-824T/-597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P=0.012) or two (P=0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.
Interleukin‐10 gene promoter polymorphism in Polish rheumatoid arthritis patients
International Journal of Immunogenetics, 2010
SummaryInterleukin (IL)‐10 is an important multifunctional cytokine with both anti‐inflammatory and immunoregulatory effects in rheumatoid arthritis (RA). In the present study, we evaluated the frequency and potential impact of IL‐10 promoter polymorphisms on susceptibility to and severity of RA in Polish in – patients with a high disease activity (mean DAS 28 C‐reactive protein 5.25). DNA was obtained from 244 RA patients and 106 healthy controls. The −592C/A and −1082G/A IL‐10 gene polymorphisms were amplified by polymerase chain reaction with restriction endonuclease mapping. The frequency of the IL‐10‐592CA, ‐592AA genotypes (respectively: 30% vs 5% and 7% vs 0%) and allele −592A (37% vs 5%) were significantly higher in RA patients as compared with a control group. We did not find any association of the IL‐10‐592C/A genotype distribution with disease parameters, except for an increased ESR (erythrocyte sedimentation rate) in patients with the −592CC genotype as compared with tho...
Medical journal of the Islamic Republic of Iran, 2022
Background: According to recent evidence, there is an association between some genetic factors and rheumatoid arthritis (RA). The aim of this study was to determine whether genetic variations in the interleukin 10 (IL10) and anti-cyclic citrullinated peptide (Anti-CCP) antibody loci were linked to RA. Methods: In this hospital-based case-control study with 224 cases and 194 healthy individuals, we investigated the association of IL-10 genotypes and anti-CCP antibodies with RA. Independent sample t, chi-square, and Fisher exact tests were used to assess the association between study variables. Results: Frequency of IL-10-1082 A/G genotype in RA patients is significantly higher than the control group (odds ratio [OR], 1.67 [95% CI, 1.11-2.51]) (p=0.009), while the frequency of IL-10-1082 A/A and G/G polymorphisms in RA patients was lower than controls and this finding for G/G polymorphism was statistically significant (p=0.01). No significant difference was observed between the 2 studied groups regarding IL-10-592 C/C, C/A, and A/A polymorphisms (p>0.05). The chance of RA occurrence among persons with positive anti-CCP was significantly (63.3 times [22.7-176.5]) higher than individuals with negative anti-CCP (p<0.001). Conclusion: According to our data, the chance of anti-CCP positivity in persons who have IL-10 genotype 1082 A/G is higher. Further studies are recommended to determine the relationship between IL-10 genotype 1082 G/A and RA. If such a relationship is proven, this finding as a diagnostic clue can help rheumatologists in the early detection of RA.
Interleukin 10 (IL-10) is an immunomodulatory cytokine that plays a central role in the pathogenesis of autoimmune diseases. Different studies consistently show increased IL-10 serum levels in rheumatoid arthritis (RA) and it appears to be caused by genetic variants. Three polymorphisms situated at positions À1082, À819 and À592 of IL10 gene and its major haplotypes have been associated with regulating IL10 promoter activity. In this study, we evaluated whether IL10 haplotypes are associated with mRNA expression and IL-10 serum levels as well as susceptibility to RA in a Western Mexican population. A total of 240 RA patients and 240 control subjects (CS) were included. Genotyping of IL10 polymorphisms was performed by PCR and PCR-RFLP, respectively. IL10 mRNA expression was determined by real-time PCR and IL-10 serum levels were measured using an ELISA kit. IL10 mRNA expression was 50-fold higher in RA patients than CS (p < 0.001), while IL-10 serum levels did not show differences between groups. However, high IL-10 serum levels were positively related to a higher seropositivity for rheumatoid factor (FR) and anti-CCP antibodies (p < 0.05). No significant differences between the distribution of haplotype frequencies were observed between both study groups, but GCC haplotype was associated with higher IL-10 serum levels compared with the ACC and ATA haplotypes in RA patients (p < 0.05). In addition, patients carrying ATA and GCC haplotypes showed higher mRNA expression than ACC (5.4-fold and 8.8-fold, respectively) and surprisingly, this trend was reversed in the controls, although it was not significant. In conclusion, our findings suggest that IL10 (GCC, ACC, and ATA) haplotypes may not be a susceptibility marker for RA in a population from Western Mexico. Nevertheless, independently of the presence of these variants, there is an aberrant overexpression of IL10 gene in RA, and it may play an important role in the pathogenesis of RA.
Clinical biochemistry, 2018
Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder of unknown etiology. IL-10 stimulates B cell survival and is involved in antibody isotype switching. The serum IL-10 levels are increased in RA patients. Ethnicity influences polymorphisms in cytokine genes. Therefore, this study was designed to explore possible association, if any, between polymorphism of IL10-1082 A/G, serum cytokine levels, inflammatory markers and gene expression in RA patients of North India. A total of 187 RA patients classified according to American college of rheumatology 2010 criteria and 214 controls were included in the study. Levels of serum IL-10 and inflammatory markers were estimated by ELISA. PCR-RFLP was used to analyze IL10-1082 A/G polymorphism. Quantitative real time PCR was used to measure the mRNA expression of IL-10 gene. The serum inflammatory markers were significantly higher in RA patients. Circulating IL-10 levels were positively and significantly correlated with RF (r = 0.28...
Trakia Journal of Science, 2015
PURPUSE: The aim of this study was to investigate the involvement of functional interleukin 10 (IL-10) and tumor necrosis factor (TNF-) promoter polymorphisms on the susceptibility to rheumatoid arthritis (RA) in Bulgarian population. METHODS: Genotyping for-1082A/G IL10 (rs1800896) and-308G/A TNFA (rs1800629) polymorphisms were performed using allele specific PCR and restriction fragment length RLFP-PCR assays, respectively, in 135 RA patients and 179 healthy controls. RESULTS: No association between the rs1800629 polymorphisms and RA risk in Bulgarian was established. In contrast, an association between rs1800896 and susceptibility to RA was demonstrated. There was an increase of the IL10-1082G allele (43% vs 36.3%, p=0.091) and a higher frequency of GG genotype (20% vs 12.8%; p =0.073) in cases versus controls. In logistic regression analysis the presence of high IL-10 producer genotype (-1082GG) was associated with 1.7 times higher risk of developing RA. When analyzing the influence of combined IL10/TNFA genotypes on RA appearance, we found that the carriage of both high cytokine producing genotypes of two polymorphisms (IL10-1082GG and TNFA-308AA/GA, respectively) significantly increased the risk of developing RA with OR=4.95 (p=0.029). CONCLUSIONS: Our result showed that IL10 rs1800896, but not TNFA rs1800629 gene polymorphism is associated with genetic predisposition to RA in Bulgarian population. However, IL10/TNFA interaction further influences RA susceptibility suggesting a genetic predisposition to abnormal immune regulation in this chronic inflammatory disorder.
Annals of the …, 2005
Objectives: To analyse the association of interleukin 10 (IL10) promoter polymorphisms, which have been shown to be related to IL10 secretion capacity, with the response to long term treatment with etanercept in patients with rheumatoid arthritis (RA). Methods: Fifty patients with active RA were treated for up to 4 years (median 39 months, range 3–52) with stable doses of etanercept as monotherapy. Treatment response was assessed as defined by the EULAR criteria in an intention to treat analysis, with the last observation carried forward. IL10 promoter microsatellite polymorphisms IL10.R and IL10.G were genotyped by fragment length analysis in patients and 189 healthy controls matched for ethnicity, age, and sex. Haplotypes were reconstructed using a method based on bayesian, coalescent theory with the PHASE software. Results: IL10 microsatellite polymorphisms were not associated with susceptibility to RA. When patients with good treatment response (n = 25) were compared with patients with moderate (n = 17) or no response (n = 8), a significantly different distribution of the prevailing alleles R2, R3 and G9, G13, respectively, became evident. Good treatment response was associated with carriage of the R3 allele or R3-G9 haplotype, whereas the allele G13 and the haplotype R2-G13 predominated in patients with moderate or no response. Conclusion: Genotyping of the IL10 promoter microsatellites may be useful in predicting the clinical response to etanercept in patients with RA. The high prevalence of the presumptive IL10 low producer allele R3 in patients with a favourable response suggests that IL10 promotes disease activity in RA under the specific condition of tumour necrosis factor antagonism.
Annals of the New York Academy of Sciences, 2007
IdentiWcation of susceptibility genes in systemic lupus erythematosus (SLE) has recently become a topic of interest. The IL-10 promoter contains three single base-pair substitutions at ¡627C > A, ¡854C > T and ¡1117G > A. These single base-pair substitutions produce three diVerent haplotypes, GCC, ACC and ATA, which aVect IL-10 expression. We examined the distribution of ¡627C > A, ¡854C > T and ¡1117G > A IL-10 promoter polymorphisms in patients with SLE (n = 103, women only) and matched controls (n = 300). Despite the higher prevalence of the GCC/GCC, GCC/ATA and ATA/ATA genotypes in SLE patients than in controls, we observed that only GCC/GCC genotype frequency distribution was signiWcant between these groups. We observed that women with the GCC/GCC genotype displayed an approximately twofold increased risk of SLE OR = 2.245 (95% CI = 1.354-3.721, P = 0.0022). We did not Wnd any associations between various genotypes of IL-10 promoter haplotypes and clinical manifestations or autoantibody production in patients with SLE. Our observations indicate that the GCC/GCC promoter genotype may contribute to SLE incidence in Polish patients.