Genetic variant of Interleukin-18 gene is associated with the Frailty Index in the English Longitudinal Study of Ageing.
Genetic variant of Interleukin-18 gene is associated with the Frailty Index in the English Longitudinal Study of Ageing.
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DOI：
10.1093/ageing/afv122
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发表时间：
2015-11
期刊：
影响因子：
6.7
通讯作者：
Pendleton N
中科院分区：
文献类型：
--
作者：
Mekli K;Marshall A;Nazroo J;Vanhoutte B;Pendleton N
背景：脆弱一词指的是老年人对应激源的易感性增加，导致体内平衡储备下降。脆弱往往会导致跌倒、住院和死亡，因此它对向老年人提供医疗保健很重要。虚弱背后的病理生理机制尚不清楚，但老年人类固醇激素分泌减少和慢性全身炎症似乎是主要原因。方法：我们使用了来自英国老龄化纵向研究的3160名年龄在50岁或以上的人的样本，并根据脆弱指数来评估他们的脆弱状况。我们选择了与类固醇激素或炎症途径有关的基因中的620个单核苷酸多态。我们进行了线性关联分析。结果变量是脆弱指数的平方根变换，年龄和性别作为协变量输入。结果：促炎症因子IL-18基因信号最强(rs360722，P=0.0021，β=−为0.015)。白介素12(rs4679868，P=0.0062，β=−0.008和rs9852519，P=0.0077，β=−0.008)、低密度脂蛋白受体相关蛋白1(rs1799986，P=0.0065，β=0.011)和选择素-P(rs6131，P=0.0097，β=−0.01)基因也有显著差异。在Bonferroni校正后，这些关联都没有显著意义。结论：我们显示了四个基因的遗传变异与脆弱指数之间的潜在关联。这些基因涉及胆固醇运输和炎症途径，因此，我们的结果进一步支持了免疫过程与老年人虚弱的关系。
Background: 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. Method: 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. Results: the strongest signal was detected in the pro-inflammatory Interleukin-18 gene (rs360722, P = 0.0021, β = −0.015). Further significant signals were observed in the Interleukin-12 (rs4679868, P = 0.0062, β = −0.008 and rs9852519, P = 0.0077, β = −0.008), low density lipoprotein receptor-related protein 1 (rs1799986, P = 0.0065, β = 0.011) and Selectin-P (rs6131, P = 0.0097, β = −0.01) genes. None of these associations remain significant after Bonferroni correction. Conclusions: 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.