The Interleukin-6 G(−174)C Promoter Polymorphism Does Not Determine Plasma Interleukin-6 Concentrations in Experimental Endotoxemia in Humans

Endler, Georg; Marsik, Claudia; Joukhadar, Christian; Marculescu, Rodrig; Mayr, Florian; Mannhalter, Christine; Wagner, Oswald; Jilma, Bernd

doi:10.1373/clinchem.2003.022459

Cited by 58 publications

(47 citation statements)

References 45 publications

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“…22 Indeed, the novel four-marker haplotype we describe here may only represent a partial elucidation of the complex regulation of IL-6, with additional upstream control regions remaining to be characterised. The IL-6 À174G4C, À572G4C, À1363G4T and À1480[CT] polymorphisms 23 In summary, our results clearly illustrate the importance of haplotypic analyses for disease associations, and that single SNP analyses are likely to provide contradictory results.…”

Section: Resultsmentioning

confidence: 98%

Novel IL-6 haplotypes and disease association

et al. 2005

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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.

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Section: Resultsmentioning

confidence: 98%

Novel IL-6 haplotypes and disease association

et al. 2005

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“…The CC genotype is considered to be a low producer and GG a high producer of IL-6 (4,7,8). However, Endler et al (6) did not find this association and Brull et al (9) found the opposite, i.e., patients with the CC allele had higher plasma IL-6 levels. Furthermore, other haplotypes cooperate with the transcriptional regulation of IL-6 influencing its production (10).…”

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confidence: 95%

“…It seems that the single-nucleotide polymorphism in the promoter region of the IL-6 gene at position -174 may regulate the plasma concentrations of IL-6 in vivo (4)(5)(6). The presence of lysine (allele C) at the guanine site (allele G) is associated with low levels of plasma IL-6 in healthy subjects.…”

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confidence: 99%

Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

Duch¹,

Figueiredo²,

Ribas³

et al. 2007

Braz J Med Biol Res

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It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

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“…The control group (group T1) included eight patients with low trauma severity; their Injury Severity Score (ISS) was between 15-20. Ten patients with moderately severe trauma (ISS of [21][22][23][24][25][26][27][28][29][30] were enrolled in group T2. Group T3 consisted of 8 patients with very severe trauma (ISS > 30).…”

Section: Patientsmentioning

confidence: 99%

Comparative Study of the Immunological Marker IL-6 and the Non-Immunological Marker PCT in Surgery Patients with Infections and Multiple Trauma

Zelzer¹,

Aigner²,

Khoschsorur³

et al. 2009

TOPATJ

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Abstract:The objective of this study was to assess and to compare the time course of the immunological signaling marker IL-6 and the non-immunological marker PCT in surgical patients with local and systemic bacterial infections and with multiple trauma of well-defined severity. 45 surgical and 26 intensive care patients were enrolled in this collaborative study. We analyzed IL-6 and PCT blood concentrations under the different experimental conditions with Cochran's Q -criterion for testing null hypotheses. For the surgical patients with local infections and with systemic infections, we did not find a significant decline of IL-6 in the time course at the confidence intervals 0.999, 0.990, and 0.950. No differences in PCT concentrations were found for the various experimental conditions. The time course of IL-6 did not change significantly with medium and high severity trauma, whereas PCT declined over time with significance levels 0.990 and 0.950. The measurement of IL-6 is predominantly a research tool at present. There are no absolute indications for routine measurements. Regarding PCT, our results do not point to this marker as a valid predictor of bacterial infections including sepsis during the early period after trauma.

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The Interleukin-6 G(−174)C Promoter Polymorphism Does Not Determine Plasma Interleukin-6 Concentrations in Experimental Endotoxemia in Humans

Cited by 58 publications

References 45 publications

Novel IL-6 haplotypes and disease association

Novel IL-6 haplotypes and disease association

Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

Comparative Study of the Immunological Marker IL-6 and the Non-Immunological Marker PCT in Surgery Patients with Infections and Multiple Trauma

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