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Genetic variant of Interleukin-18 gene is associated with the Frailty Index in the English Longitudinal Study of Ageing.

ABSTRACT: The term frailty refers to a condition of increased vulnerability to stressors among older people, leading to a decline in homeostatic reserve. Frailty often leads to falls, hospitalisation and mortality, hence its importance for the delivery of health care to older adults. The pathophysiological mechanisms behind frailty are not well understood, but the decreased steroid-hormone production and elevated chronic systemic inflammation of older people appear to be major contributors.We used a sample of 3,160 individuals aged 50 or older from the English Longitudinal Study of Ageing and assessed their frailty status according to a Frailty Index. We selected 620 single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways. We performed linear association analysis. The outcome variable was the square root transformation of the Frailty Index, with age and sex entered as covariates.The strongest signal was detected in the pro-inflammatory Interleukin-18 gene (rs360722, P = 0.0021, ? = -0.015). Further significant signals were observed in the Interleukin-12 (rs4679868, P = 0.0062, ? = -0.008 and rs9852519, P = 0.0077, ? = -0.008), low density lipoprotein receptor-related protein 1 (rs1799986, P = 0.0065, ? = 0.011) and Selectin-P (rs6131, P = 0.0097, ? = -0.01) genes. None of these associations remain significant after Bonferroni correction.We show potential associations between genetic variants of four genes and the frailty index. These genes are involved in the cholesterol transport and inflammatory pathway and, as such, our results provide further support for the involvement of the immunological processes in frailty of the elderly.

SUBMITTER: Mekli K

PROVIDER: S-EPMC4621230 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Genetic variant of Interleukin-18 gene is associated with the Frailty Index in the English Longitudinal Study of Ageing.

Mekli Krisztina K Marshall Alan A Nazroo James J Vanhoutte Bram B Pendleton Neil N

Age and ageing 20150922 6

<h4>Background</h4>The term frailty refers to a condition of increased vulnerability to stressors among older people, leading to a decline in homeostatic reserve. Frailty often leads to falls, hospitalisation and mortality, hence its importance for the delivery of health care to older adults. The pathophysiological mechanisms behind frailty are not well understood, but the decreased steroid-hormone production and elevated chronic systemic inflammation of older people appear to be major contribut ...[more]

PMID: 26396182

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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

Genetic variant of Interleukin-18 gene is associated with the Frailty Index in the English Longitudinal Study of Ageing.

Publications

Genetic variant of Interleukin-18 gene is associated with the Frailty Index in the English Longitudinal Study of Ageing.

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