Thomas Kate, Rafiq Sajjad, Frayling Timothy M, Ebrahim Shah, Kumari Meena, Gallacher John, Ferrucci Luigi, Bandinelli Stefania, Wallace Robert B, Melzer David, Martin Richard M, Ben-Shlomo Yoav
Department of Social Medicine, University of Bristol, Bristol BS8 2PS, UK.
J Gerontol A Biol Sci Med Sci. 2009 Nov;64(11):1177-82. doi: 10.1093/gerona/glp092. Epub 2009 Jul 24.
Levels of the proinflammatory cytokine interleukin-18 (IL-18) are raised in old age and are associated with reduced physical functioning. Previous studies have indicated that the C allele of the rs5744256 polymorphism in the IL-18 gene is strongly associated with reduced circulating IL-18 levels. This variant has previously been associated with improved locomotor performance in old age, but the finding requires independent replication.
We examined the association between the IL-18 polymorphism rs5744256 and physical functioning in three cohorts with a total of 4,107 participants aged 60-85 years: the English Longitudinal Study of Ageing, Caerphilly, and Boyd Orr. We meta-analyzed (N = 6,141) the results with data from the original paper reporting this association: Iowa-Established Populations for Epidemiological Study of the Elderly and InCHIANTI cohorts. Physical functioning was assessed by timed walks or the get up and go test. As locomotor performance tests differed between the cohorts and the distributions of times to complete the test (in seconds) were positively skewed, we used the reciprocal transformation and computed study-specific z scores.
Based on the three new studies, the estimated linear regression coefficient per C allele was 0.011 (95% confidence interval [95% CI]: -0.04 to 0.06). A meta-analysis that pooled the data from all studies showed weak evidence of an effect, with a regression coefficient of 0.047 (95% CI: 0.010 to 0.083).
We did not replicate an association between the IL-18 rs5744256 polymorphism and the physical function in people aged 60-85 years. However, pooling data from all studies suggested a weak association of the C allele of the rs5744256 single nucleotide polymorphism on improving walking times in old age.
促炎细胞因子白细胞介素-18（IL-18）水平在老年时升高，且与身体功能下降有关。先前的研究表明，IL-18基因中rs5744256多态性的C等位基因与循环IL-18水平降低密切相关。该变体先前已被证明与老年时运动能力的改善有关，但这一发现需要独立验证。
我们在三个队列中研究了IL-18多态性rs5744256与身体功能之间的关联，这三个队列共有4107名年龄在60 - 85岁的参与者，分别是英国老龄化纵向研究、卡菲利研究和博伊德奥尔研究。我们对这些结果与报告该关联的原始论文（爱荷华州老年人流行病学研究既定人群和基安蒂研究队列）的数据进行了荟萃分析（N = 6141）。身体功能通过定时步行或起立行走测试进行评估。由于各队列之间的运动能力测试不同，且完成测试的时间（以秒为单位）分布呈正偏态，我们使用倒数变换并计算了各研究的z分数。
基于这三项新研究，每个C等位基因的估计线性回归系数为0.011（95%置信区间[95%CI]：-0.04至0.06）。对所有研究数据进行的荟萃分析显示，有微弱的效应证据，回归系数为0.047（95%CI：0.010至0.083）。
我们未能在60 - 85岁人群中重复验证IL-18 rs5744256多态性与身体功能之间的关联。然而，汇总所有研究的数据表明，rs5744256单核苷酸多态性的C等位基因与改善老年人步行时间之间存在微弱关联。
