Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases?

Abstract

Background: A single-nucleotide polymorphism (SNP) in the promoter region of the interleukin-6 (IL-6) gene at position ؊174 (G>C) has been reported to be associated with a variety of major diseases, such as Alzheimer disease, atherosclerosis, and cardiovascular disease, cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis, and systemic-onset juvenile chronic arthritis. However, authors of previous in vitro and in vivo studies have reported conflicting results regarding the functionality of this polymorphism. We therefore aimed to clarify the role of the ؊174 SNP for the induction of IL-6 in vivo. Methods: We vaccinated 20 and 18 healthy individuals homozygous for the ؊174 C and G alleles, respectively, with 1 mL of Salmonella typhii vaccine. IL-1␤, IL-6, and tumor necrosis factor-␣ (TNF-␣) were measured in the blood at baseline and up to 24 h after vaccination. Results: Individuals with the G genotype had significantly higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did individuals with the C genotype (P <0.005). There were no differences between the two genotypes regarding serum concentrations of IL-1␤ and TNF-␣ before or after vaccination. Conclusions: The ؊174 G>C SNP in the promoter region of the IL-6 gene is functional in vivo with an increased inflammatory response associated with the G

Cancer-related fatigue: Links with inflammation in cancer patients and survivors

“…Each of these genotypes has been associated with increased expression of their respective cytokine (e.g., Brull et al, 2001;Burzotta et al, 2001;Galicia et al, 2004;di Giovine et al, 1992). We did not find an association between fatigue-related genotypes and circulating cytokine concentrations, possibly due to the small sample size and the relatively low levels of these markers in this otherwise healthy sample; it is possible that differences might have emerged following in vivo immune stimulation, as seen in previous research (e.g., Bennermo et al, 2004). These findings provide preliminary evidence that gene polymorphisms may increase risk for persistent cancer-related fatigue, presumably through effects on cytokine expression triggered by cancer and its treatment.…”

Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response

“…The correlation of elevated plasma IL-6 with low plasma zinc to gastrointestinal disease occurrence in children with Down's syndrome is an example of such reports (10). Because hypozincemia is an IL-6-dependent physiologic effect, the response may vary in individuals with single-nucleotide polymorphisms in the promoter region of IL-6, which influences IL-6 production and function (33,34). These could have implications with respect to geographic differences in manifestations of zinc deficiency.…”

Genes and the ageing muscle: a review on genetic association studies

“…Recent data also indicate a pivotal role of this protein in the processes of muscle repair and hypertrophy following exercise-induced damage (Serrano et al 2008). A functional G/C polymorphism at position −174 [rs1800795] was described in the 5′ flanking region of the IL6 (IL6) gene (Fishman et al 1998), with the G allele being associated with increased transcriptional response in vitro (Fishman et al 1998) and in vivo conditions (Bennermo et al 2004). …”