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Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing.

ABSTRACT: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic-pituitary-adrenal axis and heightened chronic systemic inflammation appear to be major contributors.We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci.The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, ? = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, ? = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant.We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results.

SUBMITTER: Mekli K

PROVIDER: S-EPMC4877432 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing.

Mekli Krisztina K Nazroo James Y JY Marshall Alan D AD Kumari Meena M Pendleton Neil N

Aging clinical and experimental research 20150807 3

<h4>Background</h4>Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic-pituitary-adrenal axis and heightened chronic systemic inflammation appear to be major contributors.<h4>Methods</h4>We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the ag ...[more]

PMID: 26248682

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Project description:BackgroundPain has been suggested to act as a stressor during aging, potentially accelerating declines in health and functioning. Our objective was to examine the longitudinal association between self-reported pain and the development, or worsening, of frailty among older men and women.MethodsThe study population consisted of 5,316 men and women living in private households in England, mean age 64.5 years, participating in the English Longitudinal Study of Ageing (ELSA). Data from Waves 2 and 6 of ELSA were used in this study with 8 years of follow-up. At Wave 2, participants were asked whether they were "often troubled with pain" and for those who reported yes, further information regarding the intensity of their pain (mild, moderate, or severe) was collected. Socioeconomic status (SES) was assessed using information about the current/most recent occupation and also net wealth. A frailty index (FI) was generated, with the presence of frailty defined as an FI >0.35. Among those without frailty at Wave 2, the association between pain at Wave 2 and frailty at Wave 6 was examined using logistic regression. We investigated whether pain predicted change in FI between Waves 2 and 6 using a negative binomial regression model. For both models adjustments were made for age, gender, lifestyle factors, depressive symptoms, and socioeconomic factors.ResultsAt Wave 2, 455 (19.7%) men and 856 (28.7%) women reported they often experienced moderate or severe pain. Of the 5,159 participants who were nonfrail at Wave 2, 328 (6.4%) were frail by Wave 6. The mean FI was 0.11 (standard deviation [SD] = 0.1) at Wave 2 and 0.15 (SD = 0.1) at Wave 6. After adjustment for age, gender, body mass index, lifestyle factors, and depressive symptoms, compared to participants reporting no pain at Wave 2 those reporting moderate (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 2.28, 4.16) or severe pain (OR = 3.78, 95% CI = 2.51, 5.71) were significantly more likely to be frail at Wave 6. This association persisted after further adjustment for either occupational class and/or net wealth level. Compared to those without pain, those with mild, moderate, or severe pain were also more likely to develop worsening frailty, as assessed using the FI, and this association persisted after adjustment for SES. There was no evidence that the association between pain and frailty was influenced by gender.ConclusionPain is associated with an increased risk and intensity of frailty in older men and women. Socioeconomic factors contribute to the occurrence of frailty; though in our study do not explain the relationship between pain and frailty.

Dataset Information

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing.

Publications

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing.

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