Interleukin-6 plasma level increases with age in an Italian elderly population ("The Treviso Longeva"aEuro"Trelong-study) with a sex-specific contribution of rs1800795 polymorphism

Interleukin-6 plasma level increases with age in an Italian elderly population ("The Treviso Longeva"aEuro"Trelong-study) with a sex-specific contribution of rs1800795 polymorphism
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DOI:
10.1007/s11357-009-9092-5
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发表时间:
2009-06-01
期刊:
AGE
影响因子:
--
通讯作者:
Forloni, Gianluigi
Forloni, Gianluigi
中科院分区:
医学2区
文献类型:
--
作者:
Albani, Diego;Batelli, Sara;Forloni, Gianluigi

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位于 IL-6 基因 (NM_000600) 5' 侧翼区域的多态性 (rs1800795) 的 C 等位基因可降低白细胞介素 6 (IL-6) 的转录率,并且 IL-6 血浆水平随着年龄的增长而增加。我们收集了意大利老年人群[“Treviso Longeva (Trelong) 研究”,年龄范围 70-106 岁,n = 668 名受试者],并评估了 rs1800795 基因型和血浆 IL-6 浓度。 rs1800795 基因型也在一项独立的意大利研究中进行了评估(“米兰”研究,年龄范围 70-96,n = 245 名受试者)。为了验证 rs1800795 基因型的年龄或性别特异性效应,我们比较了年龄小于 85 岁的人 (70-85) 和年长的人 (85+)。我们在 Trelong 研究中发现 85 岁以上男性中 rs1800795 C/C 基因型的频率显着降低,而在 Milan 研究中这一数据并未达到显着性。然而,综合考虑这两项研究,rs1800795 C/C 基因型的频率在 85 岁以上男性中显着低于 70-85 岁男性(分别为 4.0% 和 10.7%),而在女性中则保持不变。至于 IL-6 血浆水平,在控制混杂因素的多变量分析后,揭示了年龄和血浆 IL-6 浓度之间的相关性 (P < 0.0001)。与 70-85 组相比,整个 85+ 组的循环 IL-6 水平也有所增加(P < 0.05,Tukey 检验)。我们提出了与炎症反应和寿命相关的遗传变异的性别特异性模式,这与 IL-6 与年龄相关的增加一致。
The transcription rate of interleukin-6 (IL-6) can be reduced by the C-allele of a polymorphism (rs1800795) located in the 5'-flanking region of the IL-6 gene (NM_000600), and IL-6 plasma levels increase with age. We assembled an elderly Italian population ["The Treviso Longeva (Trelong) study", age range 70-106 years, n = 668 subjects] and assessed rs1800795 genotype and plasma IL-6 concentrations. The rs1800795 genotype was also assessed in an independent Italian study ("Milan" study, age range 70-96, n = 245 subjects). To verify an age- or sex-specific effect of rs1800795 genotype we compared people younger (70-85) and older (85+) than 85 years of age. We found a significant reduction in the frequency of rs1800795 C/C genotype in 85+ men from the Trelong study, while in the Milan study this data did not reach significance. However, considering the two studies together, the frequency of the rs1800795 C/C genotype was significantly lower in 85+ than in 70-85 males (4.0% and 10.7%, respectively), while it remained unchanged in females. As for IL-6 plasma levels, after a multivariate analysis to control for confounders, a correlation between age and plasma IL-6 concentrations was revealed (P < 0.0001). An increase in circulating IL-6 levels in the entire 85+ group compared to the 70-85 group (P < 0.05, Tukey's test) was also noticed. We suggest a sex-specific pattern for genetic variability linked to inflammatory response and longevity, consistent with the age-related increase in IL-6.