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

Tomàs Pinós, Noriyuki Fuku, Yolanda Cámara, Yasumichi Arai, Yukiko Abe, Gabriel Rodríguez-Romo, Nuria Garatachea, Alejandro Santos-Lozano, Elisabet Miro-Casas, Marisol Ruiz-Meana, Imanol Otaegui, Haruka Murakami, Motohiko Miyachi, David Garcia-Dorado, Kunihiko Hinohara, Antoni L. Andreu, Akinori Kimura, Nobuyoshi Hirose, Alejandro Lucia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)933-943
Number of pages11
Issue number2
Publication statusPublished - 2014 Apr
Externally publishedYes


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

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology


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