Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity

Kiymet Bozaoglu, Chantal Attard, Hemant Kulkarni, Nik Cummings, Vincent P. Diego, Melanie A. Carless, Katherine A. Shields, Matthew P. Johnson, Sudhir Kowlessur, Thomas D. Dyer, Anthony G. Comuzzie, Laura Almasy, Paul Zimmet, Eric K. Moses, Harald H.H. Göring, Joanne E. Curran, John Blangero, Jeremy B.M. Jowett

    Research output: Contribution to journalArticlepeer-review

    8 Scopus citations

    Abstract

    Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity.Thepathogeneticandclinical influences of sIL1RAP are unknown. Copyright

    Objective: The objective of the studywasto elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts.

    Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230).

    Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study.

    Results: Asignificant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM-134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 = 10=23) within the IL1RAP gene.

    Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

    Original languageEnglish (US)
    Pages (from-to)3435-3443
    Number of pages9
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume99
    Issue number9
    DOIs
    StatePublished - Sep 1 2014

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Biochemistry
    • Endocrinology
    • Clinical Biochemistry
    • Biochemistry, medical

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