The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts

Abstract

The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery disease (CAD). We compared allele/genotype distributions of rs1333049 in cases (centenarians) and controls (younger adults, without (healthy) or with CAD) in two independent cohorts: Spanish (centenarians: n = 152, 128 women, 100–111 years; healthy controls: n = 343, 212 women, age <50 years; CAD controls: n = 98, 32 women, age ≤65 years) and Japanese (centenarians: n = 742, 623 women, 100–115 years; healthy controls: n = 920, 511 women, < 60 years; CAD controls: n = 395, 45 women, age ≤65 years). The frequency of the “risk” C-allele tended to be lower in Spanish centenarians (47.0 %) than in their healthy (52.9 %, P = 0.088) or CAD controls (55.1 %, P = 0.078), and significant differences were found in genotype distributions (P = 0.034 and P = 0.045), with a higher frequency of the GG genotype in cases than in both healthy and CAD controls as well as a lower proportion of the CG genotype compared with healthy controls. In the Japanese cohort, the main finding was that the frequency of the C-allele did not differ between centenarians (46.4 %) and healthy controls (47.3 %, P = 0.602), but it was significantly lower in the former than in CAD controls (57.2 %, P < 0.001). Although more research is needed, the present and recent pioneer findings (Rejuvenation Res 13:23–26, 2010) suggest that the rs1333049 polymorphism could be among the genetic contributors to exceptional longevity in Southern European populations, albeit this association does not exist in the healthy (CAD-free) Japanese population.

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Acknowledgments

This study was funded by the Fondo de Investigaciones Sanitarias (FIS, refs. # PI12/00914, PI10/00036, and PI12/00788) and was supported in part by grants from the program “A Grant-in-Aid for Challenging Exploratory Research” (24650414 to N. Fuku) from the Ministry of Education, Culture, Sports, Science and Technology and by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan (to M. Miyachi).

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Correspondence to Alejandro Lucia.

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Tomàs Pinós and Noriyuki Fuku contributed equally.

Nobuyoshi Hirose and Alejandro Lucia share senior authorship.

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Pinós, T., Fuku, N., Cámara, Y. et al. The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts. AGE 36, 933–943 (2014). https://doi.org/10.1007/s11357-013-9593-0

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Keywords

  • Centenarians
  • Genetics
  • Coronary artery disease
  • CDKN2A
  • CDKN2B