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FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

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Abstract

Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the FNDC5 gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n = 175, 144 women) and healthy controls (n = 347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P ≤ 0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P = 0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the FNDC5 gene or in other genes involved in irisin signaling.

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Acknowledgments

This study was funded by the Fondo de Investigaciones Sanitarias (FIS, ref. # PI12/00914).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, University of Valencia and Fundación para la Investigación del Hospital Clínico Universitario (INCLIVA), Av. Blasco Ibañez, 15, Valencia, 46010, Spain

    Fabian Sanchis-Gomar & Helios Pareja-Galeano

  2. Faculty of Health and Sport Science, University of Zaragoza, Huesca, Spain

    Nuria Garatachea

  3. Research Institute of Hospital 12 de Octubre (“i+12”), Madrid, Spain

    Nuria Garatachea

  4. Biology Centre, China Institute of Sport Science, Beijing, China

    Zi-hong He & Ye Tian

  5. Graduate School of Health and Sports Science, Juntendo University, 1-1 Hiraga-gakuendai, Inzai-city, Chiba, 270-1695, Japan

    Noriyuki Fuku

  6. Center for Supercentenarian Study, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yasumichi Arai, Yukiko Abe & Nobuyoshi Hirose

  7. Department of Health Promotion and Exercise, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, 162-8636, Tokyo, Japan

    Haruka Murakami & Motohiko Miyachi

  8. European University of Madrid, Villaviciosa de Odón, 28670, Madrid, Spain

    Thomas Yvert, Catalina Santiago, Carmen Fiuza-Luces & Alejandro Lucia

  9. Department of Health Sciences, University of Pavia, Via Bassi, 21, I-27100, Pavia, Italy

    Letizia Venturini, Giovanni Ricevuti & Enzo Emanuele

  10. Hospital Universitario 12 de Octubre, Research Institute (i+12), Avda. de Córdoba s/n, 28041, Madrid, Spain

    Carmen Fiuza-Luces, Alejandro Santos-Lozano & Alejandro Lucia

  11. Department of Biomedical Science, University of León, Campus de Vegazana s/n, 24071, León, Spain

    Alejandro Santos-Lozano

  12. INEF, Universidad Politécnica de Madrid, c/ Martín Fierro s/n, 28040, Madrid, Spain

    Gabriel Rodríguez-Romo

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  1. Fabian Sanchis-Gomar
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  2. Nuria Garatachea
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  3. Zi-hong He
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  5. Noriyuki Fuku
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  6. Ye Tian
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  7. Yasumichi Arai
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  8. Yukiko Abe
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  9. Haruka Murakami
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  10. Motohiko Miyachi
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  14. Carmen Fiuza-Luces
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  18. Nobuyoshi Hirose
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  19. Enzo Emanuele
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Correspondence to Fabian Sanchis-Gomar.

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Fabian Sanchis-Gomar and Nuria Garatachea contributed equally to this paper

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Sanchis-Gomar, F., Garatachea, N., He, Zh. et al. FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs. AGE 36, 9733 (2014). https://doi.org/10.1007/s11357-014-9733-1

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