Interleukin-6 promoter polymorphism (-174 G/C) in Caucasian German patients with systemic lupus erythematosus

Schotte, Heiko; Schlüter, B.; Rust, Stephan; Aßmann, Gunter; Domschke, Wolfram; Gaubitz, M.

doi:10.1093/rheumatology/40.4.393

Cited by 81 publications

(62 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The frequency of the C allele in healthy Caucasians is 48%. 7,8 Several studies showed conflicting results regarding the effect of 2174G/C IL-6 polymorphism on plasma CRP or IL-6 levels and cardiovascular risk factors. Brull et al 9 have shown that patients carrying !1C allele of the 2572G/C and 2174G/C IL-6 polymorphisms had significantly higher IL-6 levels six hours after CABG.…”

Section: Introductionmentioning

confidence: 99%

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

et al. 2010

View full text Add to dashboard Cite

Background: The interleukin-6 (IL-6) promoter 2174G/C polymorphism (rs1800795) is associated with enhanced systemic inflammatory response to injury. However, data on the effect of this polymorphism on inflammatory markers in patients undergoing coronary artery bypass grafting surgery (CABG) are inconsistent. The aim of our study was to investigate whether 2174G/C IL-6 polymorphism affects plasma IL-6 and C-reactive protein (CRP) concentrations in patients undergoing CABG. Methods: A total of 179 consecutive white patients (77% men, aged 65 + 8.6 standard deviation [SD] y) scheduled for elective isolated CABG were studied. Pre-and postoperative CRP and IL-6 levels were analysed in relation to the 174G/C IL-6 polymorphism determined by using TaqMan single-nucleotide polymorphism genotyping technique. Results: The genotype distribution was as follows: GG -46 (26%), GC -93 (52%) and CC -40 (22%). The C allele carriers had higher baseline CRP (4.1 + 0.35 versus 2.4 + 0.59 mg/L, P ¼ 0.02) and IL-6 levels (3.0 + 0.17 versus 2.2 + 0.3 pg/mL, P ¼ 0.02) than GG patients. Five to seven days after CABG, CRP levels rose by 54% (P ¼ 0.03), and IL-6 levels tended to be higher (P ¼ 0.07) in 2174C allele carriers than the non-carriers. There were no associations between 2174G/C IL-6 polymorphism and any demographic-, clinical-or procedure-related variables as well as major adverse cardiovascular events. Multivariate regression analysis, including sex, age, body mass index, hypercholesterolaemia, smoking, hypertension diabetes, identified CG þ CC genotype as the only independent predictor of preoperative CRP and IL-6 levels. Conclusions: The presence of the 2174C allele determines to some extent higher plasma CRP and IL-6 concentrations pre-and postoperatively in CABG patients.

show abstract

Section: Introductionmentioning

confidence: 99%

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

et al. 2010

View full text Add to dashboard Cite

show abstract

“…1,2 This is in keeping with clinical findings that high serum IL-6 correlates with active disease and fever. [3][4][5] Since our first report, this variant has been associated with numerous diseases including type I and II diabetes mellitus, 6,7 SLE, 8 Sjögren's syndrome, 9 bone density and osteoporosis, [10][11][12] Alzheimer disease 13 and coronary heart disease. [14][15][16] The candidate gene approach has been widely used to analyse possible associations between genetic variants and autoimmune and inflammatory diseases, with the selection of genes by investigators based on a priori knowledge of disease pathogenesis and phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Novel IL-6 haplotypes and disease association

et al. 2005

View full text Add to dashboard Cite

Interleukin-6 (IL-6) is a pleiotropic cytokine crucial in both adaptive and innate immunity. Numerous genetic studies have shown association with variants of this gene in a multitude of diseases and phenotypes. Most tests of association have focused on a limited set of promoter polymorphisms, in particular, the À174G4C; however, there are many inconsistencies within and between these studies. We propose that there is a more complex regulatory haplotype extending further upstream of the previously characterised promoter region which will provide a more detailed view of the effect of variation on lL-6 regulation. We have exploited two additional single nucleotide polymorphisms (SNPs) in IL-6 that, when examined as a haplotype with existing markers, show an increased level of association with systemic onset juvenile arthritis in a family-based study. This suggests that the haplotype effect may be more functionally relevant to the disease.

show abstract

“…were found to be associated with SLE by population-based case-control studies 18,19,20 . Although the initiating immunological event in SLE remains unknown, it has been shown that an imbalance is involved between depressed T H 1 cell cytokines, which promote cell-mediated immunity, and enhanced T H 2 cell cytokines, which support physiological cascade 21 . Cytokines are also known to be involved in the pathogenesis of SLE.…”

Section: Discussionmentioning

confidence: 99%

“…Because the Hep3B cell line originates from human hepatocellular carcinoma and IL-6 is primarily synthesized in the liver, it is an appropriate cell line for this purpose. To replicate the Hep3B cell line results, we also tested the promoter activity in the HeLa cell line from human cervical carcinoma 21,23 . The promoter reporter structure carrying the -278 C allele displayed higher promoter activity than the structure carrying the -278 A allele in Hep3B cells and HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 6 Gene Polymorphisms Are Associated with Systemic Lupus Erythematosus in Koreans

Jeon¹,

Kim²,

Kim³

et al. 2010

J Rheumatol

View full text Add to dashboard Cite

Objective.Interleukin 6 (IL-6) gene polymorphisms are known to play a role in chronic inflammatory disorders. We searched for polymorphisms in theIL-6gene and described their pathogenic role in Korean patients with systemic lupus erythematosus (SLE).Methods.Genomic DNA was extracted from 151 patients with SLE and 151 controls, and about 1.4 kb-sizedIL-6genes located between promoter region and exon 2 region were amplified by polymerase chain reaction. The promoter activity was analyzed by luciferase reporter assay in Hep3B cells and HeLa cells.Results.We identified 4 single-nucleotide polymorphisms (SNP; −572 C > G, −278 A > C in the promoter, and 330 T > G, and 334 A > T in exon 2) and a −373 AnTntract polymorphism in theIL-6gene. The genotype frequency, −373 A10T11, −278 C, and 334 T allele were significantly associated with SLE (p < 0.001, p = 0.03 and p = 0.005, respectively). Patients with SLE carrying the −572 G allele had anti-dsDNA more frequently (p = 0.007). In addition, thrombocytopenia was significantly more common in patients carrying the −278 C allele (p = 0.006). In the haplotype analysis, patients with SLE had more frequently haplotype HT3 (CA10T11ATA, dominant model, p = 0.012) that was associated with arthritis, leukopenia, anti-dsDNA, and hypocomplementemia. Promoter reporter structures carrying the −278 C allele displayed significantly higher promoter activity than the −278 A allele in Hep3B cells (p < 0.001) and HeLa cells (p < 0.001).Conclusion.These data suggest thatIL-6gene polymorphisms are associated with disease susceptibility and phenotype of SLE. In addition, promoter polymorphisms may be involved in regulation ofIL-6expression.

show abstract

Interleukin-6 promoter polymorphism (-174 G/C) in Caucasian German patients with systemic lupus erythematosus

Abstract: The IL-6 promoter polymorphism --174 G/C does not contribute significantly to disease susceptibility, but predisposes to distinct clinical and immunological features. A genetically determined high IL-6 response may have a pathogenic role under these conditions.

Cited by 81 publications

References 41 publications

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

Novel IL-6 haplotypes and disease association

Interleukin 6 Gene Polymorphisms Are Associated with Systemic Lupus Erythematosus in Koreans

Contact Info

Product

Resources

About