Biostatistics Unit, Mayo Clinic, Jacksonville, Florida, United States of America.
PLoS One. 2012;7(8):e42877. doi: 10.1371/journal.pone.0042877. Epub 2012 Aug 13.
A variety of definitions of successful aging have been proposed, many of which relate to longevity, freedom from disease and disability, or preservation of high physical and cognitive function. Many behavioral, biomedical, and psychological factors have been linked with these various measures of successful aging, however genetic predictors are less understood. Parkinson's disease (PD) is an age-related neurodegenerative disorder, and variants in the α-synuclein gene (SNCA) affect susceptibility to PD. This exploratory study examined whether SNCA variants may also promote successful aging as defined by survival without neurological disease.
We utilized 769 controls without neurological disease (Mean age: 79 years, Range: 33-99 years) and examined the frequency of 20 different SNCA variants across age groups using logistic regression models. We also included 426 PD cases to assess the effect of these variants on PD risk.
There was a significant decline in the proportion of carriers of the minor allele of rs10014396 as age increased (P = 0.021), from 30% in controls younger than 60 to 14% in controls 90 years of age or older. Findings were similar for rs3775439, where the proportion of carriers of the minor allele declined from 32% in controls less than 60 years old to 19% in those 90 or older (P = 0.025). A number of SNCA variants, not including rs10014396 or rs3775439, were significantly associated with susceptibility to PD.
In addition to its documented roles in PD and α-synucleinopathies, our results suggest that SNCA has a role in survival free of neurological disease. Acknowledging that our findings would not have withstood correction for multiple testing, validation in an independent series of aged neurologically normal controls is needed.
已经提出了多种成功老龄化的定义，其中许多与长寿、无疾病和残疾或保持高身体和认知功能有关。许多行为、生物医学和心理因素与这些成功老龄化的各种衡量标准有关，但是遗传预测因素了解较少。帕金森病（PD）是一种与年龄相关的神经退行性疾病，α-突触核蛋白基因（SNCA）的变异会影响 PD 的易感性。这项探索性研究检查了 SNCA 变体是否也可以促进无神经疾病的生存所定义的成功老龄化。
我们利用了 769 名无神经疾病的对照者（平均年龄：79 岁，范围：33-99 岁），并使用逻辑回归模型检查了 20 种不同的 SNCA 变体在不同年龄组中的频率。我们还包括了 426 例 PD 病例，以评估这些变体对 PD 风险的影响。
随着年龄的增长，rs10014396 次要等位基因的携带者比例显着下降（P = 0.021），从 60 岁以下对照者的 30％下降到 90 岁或以上对照者的 14％。rs3775439 的结果相似，携带次要等位基因的比例从 60 岁以下的对照者的 32％下降到 90 岁或以上的对照者的 19％（P = 0.025）。除了 rs10014396 或 rs3775439 之外，许多 SNCA 变体与 PD 的易感性显着相关。
除了其在 PD 和α-突触核蛋白病中的作用外，我们的研究结果表明 SNCA 在无神经疾病的生存中起作用。鉴于我们的发现无法承受多次测试的校正，因此需要在独立的一系列年龄较大的神经正常对照中进行验证。
