Preliminary Evidence of a Genetic Association Between Chromosome 9p21.3 and Human Longevity

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.