title: Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity.
abstract: BACKGROUND
  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. The pathogenetic and clinical influences of sIL1RAP are unknown.
  
  
  OBJECTIVE
  The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts.
  
  
  METHODS
  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).
  
  
  METHODS
  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
  A significant 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.
authors.affiliation: Baker IDI Heart and Diabetes Institute (K.B., C.A., N.C., K.A.S., P.Z., J.B.M.J.), Melbourne, Victoria 3004, Australia; Texas Biomedical Research Institute (H.K., V.P.D., M.A.C., M.P.J., T.D.D., A.G.C., L.A., E.K.M., H.H.H.G., J.E.C., J.B.), San Antonio, Texas 78245-0549; and Ministry of Health and Quality of Life (S.K.), Port Louis, Mauritius.
authors.forename: Kiymet
authors.initials: K
authors.lastname: Bozaoglu
authors.forename: Chantal
authors.initials: C
authors.lastname: Attard
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.forename: Nik
authors.initials: N
authors.lastname: Cummings
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Diego
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Shields
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kowlessur
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Paul
authors.initials: P
authors.lastname: Zimmet
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Jeremy B M
authors.initials: JB
authors.lastname: Jowett
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D053577:Interleukin-1 Receptor Accessory Protein / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D008297:Male; D008436:Mauritius / Q000453:epidemiology; D017058:Mexican Americans / Q000235:genetics / Q000706:statistics & numerical data; D008875:Middle Aged; D008957:Models, Genetic; D009765:Obesity / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012995:Solubility; D013781:Texas / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C507765:IL1RAP protein, human; D053577:Interleukin-1 Receptor Accessory Protein