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首页> 外文期刊>International Journal of Molecular Epidemiology and Genetics >The SIRT1 promoter polymorphic site rs12778366 increases IL-6 related human mortality in the prospective study a??Treviso Longeva (TRELONG)a??
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The SIRT1 promoter polymorphic site rs12778366 increases IL-6 related human mortality in the prospective study a??Treviso Longeva (TRELONG)a??

机译：在前瞻性研究中，SIRT1启动子多态性位点rs12778366可增加与IL-6相关的人类死亡率。

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Studies on sirtuins (SIRT), a family of proteins with deacetylase activity, have provided convergent evidence of the key role of these enzymes in aging-linked physiological functions. The link between SIRT1 and longevity has emerged in model organism but few data are available in humans, in particular relying on longitudinal studies. Here, we assessed whether a genetic variant within SIRT1 gene promoter (rs12778366) was associated to human longevity. We analyzed 586 genomic DNA (gDNA) collected in the study “Treviso Longeva” (TRELONG), including elderly over 70 years of age from the municipality of Treviso, a town in the Northeast of Italy, with a 11-year follow-up. We genotyped SIRT1 rs12778366 by real-time polymerase chain reaction (RT-PCR) allelic discrimination assay. A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association between rs12778366 and longevity. When we performed a longitudinal analysis considering mortality as dependent variable, we did not observe an association of rs12778366 with longevity in the whole population (corrected P-value = 0.33). However, when we stratified the TRELONG subjects according to circulating level of interleukin-6 (IL-6), a predictor of disability and mortality, we found that rs12778366 (TC+CC) carriers were at increased risk of mortality in comparison to the TT reference group (corrected P-value = 0.03, HR 1.47). Our data do not support a major role of rs12778366 in human longevity, but the stratified analysis on IL-6 suggests that this variant may be involved in the detrimental effect of high circulating IL-6 in the elderly.
机译：sirtuins（SIRT）是具有脱乙酰基酶活性的蛋白质家族，其研究为这些酶在衰老相关的生理功能中的关键作用提供了越来越多的证据。 SIRT1和寿命之间的联系已在模型生物中出现，但人类的数据很少，特别是依赖于纵向研究。在这里，我们评估了SIRT1基因启动子（rs12778366）中的遗传变异是否与人类寿命有关。我们对“ Treviso Longeva”（TRELONG）研究中收集的586个基因组DNA（gDNA）进行了分析，其中包括来自意大利东北部城镇Treviso的70岁以上的老人，并进行了11年的随访。我们通过实时聚合酶链反应（RT-PCR）等位基因鉴别分析对SIRT1 rs12778366进行基因分型。通过比较85岁以上及以下年龄的人群进行的横断面分析未证明rs12778366与寿命之间存在关联。当我们进行以死亡率为因变量的纵向分析时，我们没有观察到rs12778366与整个人群的寿命相关（校正后的P值= 0.33）。但是，当我们根据白细胞介素6（IL-6）的循环水平对TRELONG受试者进行分层时，白细胞介素6（IL-6）是残障和死亡率的预测指标，我们发现rs12778366（TC + CC）携带者的死亡率比TT高参考组（校正后的P值= 0.03，HR 1.47）。我们的数据不支持rs12778366在人类寿命中的主要作用，但对IL-6的分层分析表明，该变异体可能与老年人高循环IL-6的有害作用有关。

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