title: CRP 1846G>A polymorphism increases risk of frailty.
abstract: BACKGROUND
  Frailty is a syndrome characterized by diminished ability to re-establish homeostasis in response to stress. We hypothesized that deficient allostatic responses to physiological challenges may predispose to frailty, that C-reactive protein (CRP) and its genetic determinants may be a measure of the integrity of the allostatic response, and that genetic determinants of the allostatic response determine the risk of frailty.
  
  
  METHODS
  Cross-sectional study of 3778 community-dwelling older men identified by random sampling of the Australian electoral roll. Explanatory variables included demographic, clinical, lifestyle behaviors, serum high-sensitivity CRP (hsCRP), and CRP 1444C>T and 1846G>A genotypes. These respective polymorphisms increase and decrease the basal concentration of hsCRP. The study outcome was frailty defined by a score of ≥4 on the FRAIL scale.
  
  
  RESULTS
  The mean age of participants was 77.1 years (SD: 3.6) and frailty was present in 196 (5.2%). The serum concentration of hsCRP was higher in frail than non-frail men (p<0.001), but levels varied according to genotypes. The odds of frailty increased progressively from GG to GA and AA genotypes of the CRP1846G>A gene (z=3.93, p<0.001), and were 2.43 (95%CI=1.62-3.67) times greater in men with CRP1846G>A AA compared with GG genotypes. The CRP 1444C>T was not associated with frailty.
  
  
  CONCLUSIONS
  Frail people have raised serum concentrations of CRP, presumably in response to the stress of underlying cause(s). However, frail individuals carrying the CRP1846G>A polymorphism seem less able to mount an efficient allostatic response, which may underpin their increased odds of frailty.
authors.affiliation: Western Australian Centre for Health & Ageing, Western Australian Institute for Medical Research, Australia. osvaldo.almeida@uwa.edu.au
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D003430:Cross-Sectional Studies; D016330:Frail Elderly; D006801:Humans; D008019:Life Style; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D002097:C-Reactive Protein