IL10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients

Kaluza, W.; Leirisalo‐Repo, Marjatta; Märker‐Hermann, E.; Westman, Pia; Reuss, Esther; Hug, Rosula; Mastrovic, Ksenija; Stradmann‐Bellinghausen, Beate; Granfors, Kaisa; Galle, Peter R.; Hawranek, Thomas

doi:10.1002/1529-0131(200105)44:5<1209::aid-anr205>3.0.co;2-s

Cited by 54 publications

(17 citation statements)

References 28 publications

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“…The SNPs at position Ϫ1082 and Ϫ592 were detected by specific PCR amplification and subsequent restriction enzyme digestion as described elsewhere. 10 Statistical Analysis. We log transformed the antiHBs and anti-HAV titers for the statistical analysis to obtain approximately normally distributed measures.…”

Section: Methodsmentioning

confidence: 99%

A Functional Polymorphism in the IL - 10 Promoter Influences the Response After Vaccination With HBsAg and Hepatitis A *

et al. 2005

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H epatitis B virus (HBV) vaccination is highly effective in the primary prevention of acute and chronic HBV. Nationwide vaccination programs have succeeded in reducing HBV related morbidity and mortality considerably. Hepatitis B vaccine responsiveness shows large interindividual variability. Results of a twin study have shown a strong genetic determination of the HBsAg specific immune response with 60% of the observed variability explained by genetic factors. Although there is a strong contribution of genes encoded within the major histocompatibility complex (MHC) most of the genetic effect originates from genes outside the MHC. 1 Possible candidates for immunoregulatory functions are cytokine genes and proteins involved in intracellular signaling pathways in lymphocytes.Interleukin (IL-10) is an important immunoregulatory cytokine that is produced by monocytes and lymphocytes. 2 It inhibits formation of proinflammatory cytokines like TNF-␣ in T cells and monocytes 3 and downregulates MHC class II expression in monocytes. 4 Contrary to its inhibitory function in T cells and macrophages, in B cells IL-10 stimulates the production of immunoglobulins and the expression of MHC class II antigens. 5 We and others have recently shown that approximately 50% of the observed interindividual variability in IL-10 production can be explained by genetic factors. 6,7 Some of the observed variability in IL-10 production is determined by polymorphisms in the 5Ј-flanking region of the IL-10 gene on chromosome 1 (1q31). The proximal promoter contains three biallelic single nucleotide polymorphisms (SNPs) at positions Ϫ1082 (G/ A), Ϫ819 (C/T) and Ϫ592 (C/A) bp from the transcription start site. These SNPs are closely linked and

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Section: Methodsmentioning

confidence: 99%

A Functional Polymorphism in the IL - 10 Promoter Influences the Response After Vaccination With HBsAg and Hepatitis A *

et al. 2005

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“…The SNPs at positions À1082 and À592 were detected by specific PCR amplification and subsequent restriction digestion as described elsewhere. [32][33][34] Whole blood culture. Heparinized blood was diluted 1:1 with RPMI-1640 (no additives).…”

Section: Methodsmentioning

confidence: 99%

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

et al. 2002

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Interleukin-10 (IL-10) has a critical role in the regulation of immune responses. The relative contribution of genetic and environmental factors to IL-10 production is under debate. We performed a twin study in 246 monozygotic and dizygotic twins to assess the heritability of IL-10 production after LPS stimulation in whole blood. In addition, the influence of promoter single nucleotide polymorphisms (À1082, À819 and À592) on transcriptional activity and their binding to nuclear factors was studied in luciferase reporter gene and electrophoretic mobility shift assays. IL-10 production showed a genetic determination with a heritability of 0.5. Decreasing body mass index (BMI), smoking and female gender lead to decreased IL-10 production. In monocytes, the À1082A allele showed higher binding affinity to the transcription factor PU.1 resulting in decreased transcriptional activity of À1082A promoter haplotypes. Genetic determination of IL-10 secretion is probably lower than that previously reported. Fifty percent of the observed variability explained by genetic factors. Female individuals produce less IL-10 than male subjects. Environmental factors like smoking and decreasing BMI exert suppressing effects on IL-10 production. Although the À1082A allele shows higher binding affinity to the PU.1 transcription factor and lower transcriptional activity, this polymorphism probably explains only a small fraction of the observed heritability.

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“…[12][13][14][15] A number of studies have been presented providing evidence for associations between these IL-10 promoter variants and infectious or autoimmune diseases, including meningococcal infection, fatal septicemia, systemic lupus erythematodes, reactive arthritis, psoriasis, Sjogreń s syndrome, and multiple sclerosis. 10,12,[16][17][18][19][20] So far, it has not been studied, however, whether IL-10 promoter variants influence lymphocyte proliferation upon antigen stimulation, a major regulatory function attributed to IL-10.…”

Section: Introductionmentioning

confidence: 99%

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen

et al. 2004

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Since interleukin (IL)-10 is a key mediator of immunosuppression, and immunosuppression is considered an important element of helminth infection, we studied variants of the putative IL-10 gene promoter in 337 individuals from 130 families heavily exposed to infection by the tissue nematode Onchocerca volvulus. As shown by transmission disequilibrium tests, variants of the IL-10 promoter at positions -1082(G/A), -819(C/T), and -592(C/A) in the haplotype of ATA were significantly associated with high peripheral blood cell (PBC) proliferative responses to O. volvulus antigen (OvAg). No associations were observed using phytohemagglutinin-induced PBC proliferation or with qualitative or quantitative phenotypes of onchocerciasis or onchocerciasis-related skin disease. The findings are compatible with the hypothesis that the ATA haplotype causes a decrease in IL-10 production by OvAg-reactive type-1 regulatory T-lymphocytes, thereby alleviating the suppression of other T cells. To our knowledge, this is the first time that an influence of IL-10 promoter variants is shown on the adaptive immune response.

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IL10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients

Cited by 54 publications

References 28 publications

A Functional Polymorphism in the IL - 10 Promoter Influences the Response After Vaccination With HBsAg and Hepatitis A *

A Functional Polymorphism in the IL - 10 Promoter Influences the Response After Vaccination With HBsAg and Hepatitis A *

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen

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