Are differences in interleukin 10 production associated with joint damage?

Huizinga, Tom W J; Keijsers, V.; Yanni, G.; Hall, M. Craig; Ramage, W.; Lanchbury, Jerry S.; Pitzalis, Costantino; Drossaers-Bakker, Wiepke; Westendorp, Rudi G.J.; Breedveld, F. C.; Panayi, G. S.; Verweij, C. L.

doi:10.1093/rheumatology/39.11.1180

Cited by 88 publications

(68 citation statements)

References 38 publications

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“…A correlation between the IL-10 alleles and the rate of joint destruction in RA patients was reported in a previous study by our group (30). In that small study, the -1082 GG haplotype was associated with high progression of joint damage in RA patients compared with -1082 AA carriers.…”

Section: Discussionsupporting

confidence: 64%

Association of the –2849 interleukin‐10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis

Lard¹,

Gaalen²,

Schonkeren³

et al. 2003

Arthritis & Rheumatism

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Objective. To analyze the -2849 A/G interleukin-10 (IL-10) promoter polymorphism, which is associated with high (AG/GG) and low (AA) IL-10 production, in a cohort of rheumatoid arthritis (RA) patients and controls in order to gain a better understanding of its role in the incidence and progression of RA.Methods. Allele frequencies of the promoter polymorphism -2849 A/G and carriage rates were compared in 283 RA patients, 413 patients with other rheumatic diseases, and 1,220 healthy controls. The rate of joint damage and baseline levels of IgG and IgM rheumatoid factors and anti-citrullinated peptide antibodies were measured and were correlated with the IL-10 gene polymorphism. Furthermore, the correlation between the invasiveness of fibroblast-like synoviocytes (FLS) and the ؊2849 IL-10 genotype was tested.

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Section: Discussionsupporting

confidence: 64%

Association of the –2849 interleukin‐10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis

Lard¹,

Gaalen²,

Schonkeren³

et al. 2003

Arthritis & Rheumatism

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“…It is possible that the alteration in IL10 response is due to synergy between the promoter and the 3′UTR, and clarification of the molecular mechanism will require further studies. This is the first reported association of the 3′UTR SNP with an asthma phenotype, and combined with the evidence of mRNA half-life determining IL10 level, could support a post-transcriptional alteration of function with this SNP [Huizinga et al, 2000]. Functional studies of the promoter SNPs and the 3′UTR SNP may elucidate the modulation of the inflammatory response by IL10 and demonstrate an important control point for potential therapeutic intervention in asthma.…”

Section: Discussionmentioning

confidence: 53%

“…Murine studies show constitutive IL10 transcription and post-transcriptional regulation, allowing for very rapid control of this cytokine [Moore et al, 2001]. IL10 release has been shown to be proportional to mRNA levels, further suggesting post-transcriptional regulation [Huizinga et al, 2000;Powell et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

IL10 gene polymorphisms are associated with asthma phenotypes in children

Lyon

Lange

Lake

et al. 2004

Genetic Epidemiology

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IL10 is an anti-inflammatory cytokine that has been found to have lower production in macrophages and mononuclear cells from asthmatics. Since reduced IL10 levels may influence the severity of asthma phenotypes, we examined IL10 single-nucleotide polymorphisms (SNPs) for association with asthma severity and allergy phenotypes as quantitative traits. Utilizing DNA samples from 518 Caucasian asthmatic children from the Childhood Asthma Management Program (CAMP) and their parents, we genotyped six IL10 SNPs: 3 in the promoter, 2 in introns, and one in the 3′ UTR. Using family-based association tests, each SNP was tested for association with asthma and allergy phenotypes individually. Population-based association analysis was performed with each SNP locus, the promoter haplotypes and the 6-loci haplotypes. The 3′ UTR SNP was significantly associated with FEV 1 as a percent of predicted (FEV 1 PP) (P=0.0002) in both the family and population analyses. The promoter haplotype GCC was positively associated with IgE levels and FEV 1 PP (P=0.007 and 0.012, respectively). The promoter haplotype ATA was negatively associated with lnPC 20 and FEV 1 PP (P=0.008 and 0.043, respectively). Polymorphisms in IL10 are associated with asthma phenotypes in this cohort. Further studies of variation in the IL10 gene may help elucidate the mechanism of asthma development in children. Keywordsinterleukin 10 (IL10); single nucleotide polymorphism (SNP); genetic association; family-based association test (FBAT); haplotype; promoter; 3′; untranslated region (3′UTR)

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“…The À1082A allele either alone 33 or in the haplotypic combination À1082A/À819T/À592A 48 was shown to be associated with a low IL10 production. Other studies reported instead an association of À1082 A with a high IL10 production 49 or were not able to detect any association. 50 Moreover À1082A is part of the same haplotypic combination as -3533T/À2828G/À2726C shown to be associated with a high IL10 production.…”

Section: Discussionmentioning

confidence: 88%

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

et al. 2002

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Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position À1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5 0 flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibiliy.

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Are differences in interleukin 10 production associated with joint damage?

Abstract: Both the immunogenetic and the synovial biopsies suggest that a variation in IL-10 production is associated with joint destruction.

Cited by 88 publications

References 38 publications

Association of the –2849 interleukin‐10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis

Association of the –2849 interleukin‐10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis

IL10 gene polymorphisms are associated with asthma phenotypes in children

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

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