Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Invest Ophthalmol Vis Sci. 2022 May 2;63(5):30. doi: 10.1167/iovs.63.5.30.
Relative telomere length (RTL) is a biomarker for physiological aging. Premature shortening of telomeres is associated with oxidative stress, which is one possible pathway that might contribute to age-related macular degeneration (AMD). We therefore aimed to investigate the association between RTL and AMD in a well-characterized group of elderly individuals.
We measured RTL in participants of the AugUR study using a multiplex quantitative PCR-based assay determining the ratio between the telomere product and a single-copy gene product (T/S ratio). AMD was assessed by manual grading of color fundus images using the Three Continent AMD Consortium Severity Scale.
Among the 2262 individuals 70 to 95 years old (627 with AMD and 1635 without AMD), RTL was significantly shorter in individuals with AMD compared to AMD-free participants. In age- and sex-adjusted logistic regression analyses, we observed an 8% higher odds for AMD per 0.1 unit shorter RTL (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.02-1.14; P = 0.005). The estimates remained stable when adjusted for smoking, high-density lipoprotein cholesterol, cardiovascular disease, diabetes, and hypertension. Interestingly, this association was only present in women (OR = 1.14; 95% CI, 1.06-1.23; P < 0.001), but not in men (OR = 1.01; 95% CI, 0.93-1.10; P = 0.76). A significant sex-by-RTL interaction on AMD was detected (P = 0.043).
Our results show an association of RTL with AMD that was restricted to women. This is in line with altered reactive oxygen species levels and higher telomerase activity in women and provides an indication for a sex-differential pathway for oxidative stress and AMD.
相对端粒长度（RTL）是生理衰老的生物标志物。端粒的过早缩短与氧化应激有关，这可能是导致年龄相关性黄斑变性（AMD）的途径之一。因此，我们旨在研究在一组特征明确的老年个体中 RTL 与 AMD 之间的关联。
我们使用基于多重定量 PCR 的测定法测量了 AugUR 研究参与者的 RTL，该测定法确定了端粒产物与单拷贝基因产物之间的比率（T/S 比率）。使用三大陆 AMD 联盟严重程度量表通过手动分级彩色眼底图像评估 AMD。
在 2262 名 70 至 95 岁的个体（627 名患有 AMD，1635 名无 AMD）中，患有 AMD 的个体的 RTL 明显短于无 AMD 参与者。在年龄和性别调整的逻辑回归分析中，我们观察到 RTL 每缩短 0.1 个单位，AMD 的几率增加 8%（优势比 [OR] = 1.08；95%置信区间 [CI]，1.02-1.14；P = 0.005）。当调整吸烟、高密度脂蛋白胆固醇、心血管疾病、糖尿病和高血压时，这些估计值仍然稳定。有趣的是，这种关联仅存在于女性中（OR = 1.14；95%CI，1.06-1.23；P <0.001），而不存在于男性中（OR = 1.01；95%CI，0.93-1.10；P = 0.76）。检测到 AMD 上 RTL 的性别-交互作用具有统计学意义（P = 0.043）。
我们的结果显示 RTL 与 AMD 之间存在关联，这种关联仅限于女性。这与女性中活性氧水平改变和端粒酶活性升高一致，并为氧化应激和 AMD 的性别差异途径提供了证据。
