Preliminary Evidence of a Genetic Association Between Chromosome 9p21.3 and Human Longevity
Preliminary Evidence of a Genetic Association Between Chromosome 9p21.3 and Human Longevity
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DOI：
10.1089/rej.2009.0970
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发表时间：
2010-02-01
影响因子：
2.6
通讯作者：
Geroldi, Diego
中科院分区：
文献类型：
--
作者：
Emanuele, Enzo;Fontana, Jacopo M.;Geroldi, Diego
背景：新的证据表明，人类长寿有一个重要的遗传因素。位于染色体9p21.3上并由单核苷酸多态性（SNP）rs 1333049（G/C）标记的一个或多个遗传变异是年龄相关疾病的主要风险因素，包括急性心肌梗死（AMI），中风和痴呆。我们假设这个基因座可能对衰老表型有广泛的影响，因此，影响实现长寿和健康生活的能力。目的：本研究的目的是评估rs 1333049多态性是否与人类寿命相关。我们检测了80名健康百岁老人的rs 1333049多态性研究对象为218名年龄小于40岁的AMI患者，以及258名年龄和性别与AMI患者相匹配的健康青年志愿者。与年轻对照组相比，百岁老人rs 1333049的C等位基因频率显著降低，而AMI患者的频率较高。在调整性别和传统血管危险因素后，rs 1333049的C等位基因仍然与达到长寿的可能性降低显著相关：比值比（OR）0.64，95%置信区间（CI）0.39-0.89，p <0.01。我们的数据表明，9p21.3的rs 1333049多态性可能会影响人类的成功长寿，可能是通过调节年龄相关疾病的风险。
Background: Emerging evidence suggests that there is a significant genetic component to human longevity. One or more genetic variants located on chromosome 9p21.3 and tagged by the single-nucleotide polymorphism (SNP) rs1333049 (G/C) are major risk factors for age-related disorders, including acute myocardial infarction (AMI), stroke, and dementia. We hypothesized that this locus may have widespread effects on aging phenotypes and, as such, influences the ability to achieve a long and healthy life.Aim: The aim of this study was to assess whether the rs1333049 polymorphism is associated with human longevity.Methods: We tested the rs1333049 polymorphism in a sample of 80 healthy centenarians (39 men and 41 women, aged 100-104), 218 patients younger than 40 who experienced an AMI, and a control group of 258 healthy young volunteers matched to AMI patients for age and sex.Results: The frequency of the C allele of rs1333049 was significantly lower in centenarians compared to young controls, whereas AMI patients showed a higher frequency. After adjustment for gender and traditional vascular risk factors, the C allele of rs1333049 remained significantly associated with a reduced likelihood to reach longevity: Odds ratio (OR) 0.64, 95% confidence interval (CI) 0.39-0.89, p < 0.01.Conclusions: Our data suggest that the rs1333049 polymorphism at 9p21.3 may influence successful human longevity, possibly by modulating the risk of age-related disorders.