Association of extended interleukin-10 promoter haplotypes with disease susceptibility and manifestations in German patients with systemic lupus erythematosus

Schotte, Heiko; Willeke, P.; Becker, H; Poggemeyer, J; Gaubitz, M.; Schmidt, Hartmut; Schlüter, B.

doi:10.1177/0961203314522334

Cited by 11 publications

(9 citation statements)

References 54 publications

(86 reference statements)

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“…As in previous studies, complexity of the IL-10 promoter with respect to functional aspects is reflected by the fact that the observed associations are generally stronger when the analysis is extended to haplotypes [ 31 ]. Thus, substantial information is gained when the structure of genetic elements is resolved to haplotypes rather than being restricted to the single nucleotide polymorphisms.…”

Section: Discussionmentioning

confidence: 83%

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Putative IL-10 Low Producer Genotypes Are Associated with a Favourable Etanercept Response in Patients with Rheumatoid Arthritis

Schotte

Schlüter²,

Schmidt³

et al. 2015

PLoS ONE

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Outcome predictors of biologic therapeutic drugs like TNF inhibitors are of interest since side effects like serious infections or malignancy cannot be completely ruled out. Response rates are heterogeneous. The present study addressed the question whether in patients with rheumatoid arthritis (RA) interleukin-10 (IL-10) promoter genotypes with potential relevance for IL-10 production capacity are associated with response to long-term treatment with etanercept. Caucasian RA patients that, according to the EULAR criteria, responded well (n = 25), moderately (n = 17) or not (n = 8) to etanercept therapy (median 36 months, range 4–52), and 160 matched controls were genotyped for the IL-10 promoter SNPs -2849 G>A (rs6703630), -1082 G>A (rs1800896), -819 C>T (rs1800871) and -592 C>A (rs1800872). Haplotypes were reconstructed via mathematic model and tested for associations with disease susceptibility and therapy response. We identified the four predominant haplotypes AGCC, GATA, GGCC, and GACC in almost equal distribution. Patients that responded well carried the putative IL-10 low producer allele -2849 A or the haplotypes AGCC and GATA (RR 2.1 and 4.0, respectively; 95% CI 1.1–4.0 and 1.1–14.8), whereas an unfavourable response was associated with carriage of the putative high producer haplotype GGCC (RR 1.9, 95% CI 1.1–3.3). No significant associations of alleles or haplotypes with disease susceptibility were observed. In RA, a low IL-10 production which is genetically determined rather by haplotypes than by SNPs may favour the response to etanercept treatment. Iatrogenic blockade of TNF may reveal proinflammatory effects of its endogeneous antagonist IL-10. Further studies are needed to correlate these genetic findings to direct cytokine measurements.

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Section: Discussionmentioning

confidence: 83%

“…BigDye 3.1 standard DNA-sequencing reactions were performed in a Gene Amp PCR System 9700, followed by capillary electrophoresis done on an ABI 3730XL sequencer (Applied Biosystems, Weiterstadt, Germany). Raw data analyses and the call of SNPs were done with the SeqScape v2.7 software (Applied Biosystems, Weiterstadt Germany) [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Putative IL-10 Low Producer Genotypes Are Associated with a Favourable Etanercept Response in Patients with Rheumatoid Arthritis

Schotte

Schlüter²,

Schmidt³

et al. 2015

PLoS ONE

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show abstract

“…(2014) reported that the GGCC haplotype was protective against SLE in a German population. 16 They constructed haplotypes using one SNP (IL-10-2849A/G) from the distal region of IL-10 promoter. However, haplotypes containing proximal promoter polymorphisms (−1082, −819, −592) did not show a significant difference between patient and control groups in a German population.…”

Section: Resultsmentioning

confidence: 99%

“…15 SNPs in both distal (3575 T/A, −2849 G/A, −2763 C/A) and proximal regions (−1082 A/G, −819 T/C, −592 C/A) have been reported to influence disease susceptibility among different populations. 6,16 Nevertheless, polymorphisms (−1082A/G, −819T/C, −592C/A) from proximal regions are abundantly studied. However, the results describing genotypic and haplotype analysis are inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients

Umare

Pradhan

Dadheech

et al. 2020

Lupus

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Single nucleotide polymorphisms in cytokine genes including interleukin-10 have been described to play a vital role in the overall pathogenesis of systemic lupus erythematosus. However, due to a lack of evidence from the Indian population, this study was conducted to analyse the possible influence of interleukin-10 promoter polymorphisms over the disease susceptibility, serum interleukin-10 level and clinical manifestations of the disease in Indian systemic lupus erythematosus patients. In total, 200 systemic lupus erythematosus patients and 201 controls were recruited under this study. Genotyping of interleukin-10 (−1082A/G; −819T/C and −592C/A) polymorphisms was done by direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods respectively. Serum interleukin-10 levels were measured by multiplex assay. Interleukin-10 −1082G and −592A allele frequencies were significantly increased in systemic lupus erythematosus patients (corrected p value <0.05). Also, combined −1082AG+GG, −819TC+CC and −592CA+AA genotype frequencies were significantly increased in the patient group. A higher trend of association between −1082AG+GG genotype frequency was observed in patients with serositis (odds ratio = 2.7, p = 0.0233, corrected p value = 0.2097). Serum interleukin-10 levels were significantly higher in systemic lupus erythematosus patients (4.3 ± 3.1 pg/ml) than controls (2.6 ± 1.4 pg/ml) ( p < 0.0001). Furthermore, interleukin-10 levels were positively correlated with disease activity ( p = 0.39, p < 0.0001). The frequency of the GCA (−1082, −819, −592) haplotype was significantly higher in systemic lupus erythematosus patients (10.6%) than controls (1.6%) (odds ratio = 5.4, p = 0.0330). Moreover, ACC, GCC and GCA haplotypes were found to be strongly associated with serositis. However, the frequency of the ACC haplotype was significantly higher in patients with neurologic involvement (odds ratio = 14.9, corrected p value <0.001). Thus, interleukin-10 promoter polymorphisms suggest they have a proactive role in increased susceptibility to the disease among Indian systemic lupus erythematosus patients.

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“…Previous studies have also shown that the IL-10 -1082G/A gene polymorphism is associated with several types of chronic inflammatory diseases, including systemic lupus erythematosus, rheumatoid arthritis, deep venous thrombosis, and sepsis (Zhang et al, 2011;Ouyang et al, 2013;Schotte et al, 2014;Tang et al, 2014). Zhang et al (2011) reported that the A allele of IL-10 -1082A/G polymorphism was associated with an increased risk of rheumatoid arthritis in a Chinese population.…”

Section: Discussionmentioning

confidence: 97%

Association between polymorphisms in the interleukin-10 gene and risk of abdominal aortic aneurysm

Wang¹,

Qq²,

Cl³

et al. 2015

Genet. Mol. Res.

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Association of extended interleukin-10 promoter haplotypes with disease susceptibility and manifestations in German patients with systemic lupus erythematosus

Abstract: Our data confirm that the complexity of the IL-10 promoter evokes the need for a meticulous analysis of its haplotypic structure in order to specify disease associations, particularly under functional aspects, thereby shedding light on the pathophysiology of SLE.

Cited by 11 publications

References 54 publications

Putative IL-10 Low Producer Genotypes Are Associated with a Favourable Etanercept Response in Patients with Rheumatoid Arthritis

Putative IL-10 Low Producer Genotypes Are Associated with a Favourable Etanercept Response in Patients with Rheumatoid Arthritis

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients

Association between polymorphisms in the interleukin-10 gene and risk of abdominal aortic aneurysm

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