Shorter telomeres are associated with mortality in those with APOE ε4 and dementia
Shorter telomeres are associated with mortality in those with APOE ε4 and dementia
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DOI：
10.1002/ana.20894
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发表时间：
2006-08-01
影响因子：
11.2
通讯作者：
Mayeux, Richard
中科院分区：
文献类型：
--
作者：
Honig, Lawrence S.;Schupf, Nicole;Mayeux, Richard
目的：端粒长度减少可能是生物衰老的标志。因此，我们假设端粒长度可能与痴呆和死亡风险增加有关。方法：该巢式病例对照研究使用了257人（平均年龄81.4±7.9岁，64.6%为女性，44.7%为西班牙裔，33.5%为非西班牙裔黑人，21.8%为非西班牙裔白人）储存的白细胞DNA。我们的实验采用实时聚合酶链反应，有两个单独的反应扩增端粒序列和参考单拷贝基因（核糖体-蛋白- po），提供计算的端粒与单拷贝基因（T/S）比率。结果：随访期间死亡患者的端粒平均长度短于存活患者（0.453 +/- 0.211 vs 0.525 +/- 0.226[+/-标准差]；p < 0.009）。与对照组相比，阿尔茨海默病患者的寿命也较短（0.458 +/- 0.207 vs 0.516 +/- 0.229; p < 0.03）。对于阿尔茨海默病患者，与端粒最长的患者相比，端粒长度中等的患者的死亡率比值比（OR）为4.8(95%置信区间[CI]， 1.7-13.8)，端粒最短的患者的死亡率比值比（OR）为7.3 （95% CI, 2.4-22.0）。epsilon 4等位基因的存在也增加了死亡率OR，中端粒的OR为5.8 (95% CI, 1.3-26.4)，最短端粒的OR为9.0 （95% CI, 1.9-41）。解释：我们的研究结果表明，白细胞端粒长度与痴呆和死亡率有关，可能是生物衰老的标志。
Objective: Reduced telomere length may be a marker of biological aging. We hypothesized that telomere length might thus relate to increased risk for dementia and mortality.Methods: This nested case-control study used stored leukocyte DNA from 257 individuals (mean age, 81.4 +/- 7.9 years; 64.6% female; 44.7% Hispanic, 33.5% non-Hispanic black, and 21.8% non-Hispanic white). Our assay used real-time polymerase chain reaction, with two separate reactions amplifying telomere sequence and reference single copy gene (ribosomal-protein-PO), providing a calculated telomere-to-single copy gene (T/S) ratio.Results: Mean telomere length was shorter among subjects dying during follow-up than in those surviving (0.453 +/- 0.211 vs 0.525 +/- 0.226 [+/- standard deviation]; p < 0.009). It was also shorter in those with Alzheimer's disease compared with control subjects (0.458 +/- 0.207 vs 0.516 +/- 0.229; p < 0.03). For participants with Alzheimer's disease, compared with those with the longest telomeres, the mortality odds ratio (OR) was 4.8 (95% confidence interval [CI], 1.7-13.8) in those with intermediate-length telomeres and 7.3 (95% CI, 2.4-22.0) in those with the shortest telomeres. The presence of an epsilon 4 allele also increased the mortality OR, with an OR of 5.8 (95% CI, 1.3-26.4) for intermediate-length telomeres and an OR of 9.0 (95% CI, 1.9-41) for the shortest telomeres.Interpretation: Our findings suggest that leukocyte telomere length is related to both dementia and mortality and may be a marker of biological aging.