CRP 1846G>A polymorphism increases risk of frailty

Maturitas. 2012 Mar;71(3):261-6. doi: 10.1016/j.maturitas.2011.11.022. Epub 2011 Dec 20.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Australia / epidemiology
  • C-Reactive Protein / analysis
  • C-Reactive Protein / genetics*
  • Cross-Sectional Studies
  • Frail Elderly*
  • Humans
  • Life Style
  • Male
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • Risk


  • C-Reactive Protein