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

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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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Authors and Affiliations

  1. Departament de Patología Mitocondrial i Neuromuscular, Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Tomàs Pinós, Yolanda Cámara & Antoni L. Andreu

  2. Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Noriyuki Fuku

  3. Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Yasumichi Arai, Yukiko Abe & Nobuyoshi Hirose

  4. INEF, Universidad Politécnica, Madrid, Spain

    Gabriel Rodríguez-Romo

  5. Facultad de Ciencias de la Salud y del Deporte, Universidad de Zaragoza, Huesca, Spain

    Nuria Garatachea

  6. Departmento de Ciencias Biomédicas, Universidad de León, León, Spain

    Alejandro Santos-Lozano

  7. Departamento de Cardiología, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Elisabet Miro-Casas, Marisol Ruiz-Meana, Imanol Otaegui & David Garcia-Dorado

  8. Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan

    Haruka Murakami & Motohiko Miyachi

  9. Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Kunihiko Hinohara & Akinori Kimura

  10. Universidad Europea and Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Madrid, Spain

    Alejandro Lucia

  11. CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain

    Tomàs Pinós, Yolanda Cámara & Antoni L. Andreu

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  1. Tomàs Pinós
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  2. Noriyuki Fuku
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  8. Alejandro Santos-Lozano
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  15. Kunihiko Hinohara
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  18. Nobuyoshi Hirose
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  19. Alejandro Lucia
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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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  • DOI: https://doi.org/10.1007/s11357-013-9593-0

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