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.
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.
Authors: Rubén Rabaneda-Bueno; Norma Torres-Carrillo; José Alberto Ávila-Funes; Luis Miguel Gutiérrez-Robledo; Thalía Gabriela Pérez-Suárez; José Luis Acosta; Sara Torres-Castro; Ana Lilia Fletes-Rayas; Itzae Gutierrez-Hurtado; Elena Sandoval-Pinto; Rosa Cremades; Nora Magdalena Torres-Carrillo Journal: Mol Biol Rep Date: 2021-02-21 Impact factor: 2.316
Authors: Paulina Zabielska; Sylwia Wieder-Huszla; Izabela Gutowska; Anna Lubkowska; Anna Knyszyńska; Anna Jurczak Journal: Int J Environ Res Public Health Date: 2019-05-30 Impact factor: 3.390
Authors: Osvaldo P Almeida; Leon Flicker; Stephen Fenner; Kate Smith; Zoe Hyde; David Atkinson; Linda Skeaf; Roslyn Malay; Dina LoGiudice Journal: PLoS One Date: 2014-04-16 Impact factor: 3.240
Authors: Krisztina Mekli; James Y Nazroo; Alan D Marshall; Meena Kumari; Neil Pendleton Journal: Aging Clin Exp Res Date: 2015-08-07 Impact factor: 3.636