2013
DOI: 10.1038/gene.2013.38
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A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

Abstract: The main genetic determinant of soluble IL-6R levels is the missense variant rs2228145, which maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ~20 ng/ml and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels… Show more

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Cited by 28 publications
(35 citation statements)
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“…IL-6R can regulate the synthesis and release of C-reactive protein in response to IL-6, suggesting that functional effects of rs12083537 may have a role in influencing IL-6R expression. A study of two large cohorts reported that the rs12083537 allele A was associated with a slightly increased sIL-6R level and a higher risk of asthma (Revez et al, 2013). However, in the present study, we detected a slight increase in sIL-6R levels for rs12083537 AG carriers compared to those levels in AA carriers, although this difference failed to achieve statistical significance.…”
Section: The Rs12083537 G Is Associated With Decreased Lung Functioncontrasting
confidence: 84%
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“…IL-6R can regulate the synthesis and release of C-reactive protein in response to IL-6, suggesting that functional effects of rs12083537 may have a role in influencing IL-6R expression. A study of two large cohorts reported that the rs12083537 allele A was associated with a slightly increased sIL-6R level and a higher risk of asthma (Revez et al, 2013). However, in the present study, we detected a slight increase in sIL-6R levels for rs12083537 AG carriers compared to those levels in AA carriers, although this difference failed to achieve statistical significance.…”
Section: The Rs12083537 G Is Associated With Decreased Lung Functioncontrasting
confidence: 84%
“…In a recent study by Revez, J.A., et al, the functional IL6R polymorphisms rs12083537 G were found to increase asthma risk (OR = 1.039, p = 0.0419) (Revez et al, 2013). However, in the present study, the variants showed a null association with asthma risk (OR = 0.87, p = 0.47).…”
Section: No Significant Differences Were Detected Between Asthmatics contrasting
confidence: 61%
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“…Although some previous studies found no association of rs2228145 with overall IL6R RNA expression (IL6R Genetics Consortium and Emerging Risk Factors Collaboration. 2012) or expression of the RNA transcript encoding mIL-6R (Ferreira et al 2013), a positive association has been reported for the rs2228145 C allele and expression level of the alternatively spliced mRNA (Ferreira et al 2013; Stephens et al 2012), and we and others found a negative association between the rs2228145 C allele and overall expression level (Revez et al 2013). …”
Section: Introductionsupporting
confidence: 66%
“…Subsequently, IL-6 signaling through the trans pathway has been thought to be more inflammatory in nature than classical signaling, in part relating to the ability of IL-6 to signal through cells that express the gp130 receptor complex but do not basally express IL-6R (76). A similar paradigm was demonstrated in allergic asthma: Th2 expansion appears to be driven by trans signaling whereby expansion of Tregs was limited by classical IL-6 signaling, and inhibition with anti-IL-6R mAb resulted in increased numbers of Tregs (77), and an increase in asthma risk was associated with a single nucleotide polymorphism that results in an increase in soluble IL-6R and trans signaling (78). Appreciation of the mechanisms by which a cytokine can mediate differential effects is critical to understanding both disease pathophysiology and effective clinical translation of therapeutics.…”
Section: Heterogeneity Of Effect Conferred By Cellular Targetmentioning
confidence: 92%