Human longevity and 11p15.5: A study in 1321 centenarians

Francesco Lescai, Helene Blanché, Almut Nebel, Marian Beekman, Mourad Sahbatou, Friederike Flachsbart, Eline Slagboom, Stefan Schreiber, Sandro Sorbi, Giuseppe Passarino, Claudio Franceschi

Research output: Contribution to journalArticle

Abstract

The 11p15.5 chromosomal region (2.8Mb) is of particular interest as it encloses five genes (HRAS1, SIRT3, TH, INS and IGF2), the variability of which was found to be associated with life extension by association studies. Mostly important, the above genes are homologous of genes that modulate lifespan in model organisms. We scanned the area in four European sample groups for a total of 1321 centenarians and 1140 younger subjects, who shared with centenarians ethnicity and geographical origin, with a set of 239 SNPs. No significant results (P <0.05) have been found on the earlier associated loci (ie, TH, IGF2, INS and HRAS1), and this study could not confirm the earlier findings on each of those genes. A meta-analysis was carried out on the SIRT3 SNP data; a total number of 2461 samples were included, but no positive association was found except for one SNP having a significant effect (rs939915). The same meta-analysis approach has been applied to the other 229 markers, and six SNPs have been found significant for the frequent genotype (rs4073591, DEAF1-rs4073590, KRTAP5-6-rs11040489, rs4930001, TSPAN32-rs800140 and rs16928120). This experience, although unable to confirm the earlier findings of the literature, highlights all the common difficulties of such studies in human longevity. Despite the rather negative findings presented here, the results derived from unprecedented studies involving such a large number of centenarians should be disseminated, thus contributing to set up adequate strategies to disentangle complex and likely heterogeneous phenotypes.

Original languageEnglish
Pages (from-to)1515-1519
Number of pages5
JournalEuropean Journal of Human Genetics
Volume17
Issue number11
DOIs
Publication statusPublished - 2009

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Single Nucleotide Polymorphism
Genes
Meta-Analysis
Life Expectancy
Genotype
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Lescai, F., Blanché, H., Nebel, A., Beekman, M., Sahbatou, M., Flachsbart, F., ... Franceschi, C. (2009). Human longevity and 11p15.5: A study in 1321 centenarians. European Journal of Human Genetics, 17(11), 1515-1519. https://doi.org/10.1038/ejhg.2009.54

Human longevity and 11p15.5 : A study in 1321 centenarians. / Lescai, Francesco; Blanché, Helene; Nebel, Almut; Beekman, Marian; Sahbatou, Mourad; Flachsbart, Friederike; Slagboom, Eline; Schreiber, Stefan; Sorbi, Sandro; Passarino, Giuseppe; Franceschi, Claudio.

In: European Journal of Human Genetics, Vol. 17, No. 11, 2009, p. 1515-1519.

Research output: Contribution to journalArticle

Lescai, F, Blanché, H, Nebel, A, Beekman, M, Sahbatou, M, Flachsbart, F, Slagboom, E, Schreiber, S, Sorbi, S, Passarino, G & Franceschi, C 2009, 'Human longevity and 11p15.5: A study in 1321 centenarians', European Journal of Human Genetics, vol. 17, no. 11, pp. 1515-1519. https://doi.org/10.1038/ejhg.2009.54
Lescai F, Blanché H, Nebel A, Beekman M, Sahbatou M, Flachsbart F et al. Human longevity and 11p15.5: A study in 1321 centenarians. European Journal of Human Genetics. 2009;17(11):1515-1519. https://doi.org/10.1038/ejhg.2009.54
Lescai, Francesco ; Blanché, Helene ; Nebel, Almut ; Beekman, Marian ; Sahbatou, Mourad ; Flachsbart, Friederike ; Slagboom, Eline ; Schreiber, Stefan ; Sorbi, Sandro ; Passarino, Giuseppe ; Franceschi, Claudio. / Human longevity and 11p15.5 : A study in 1321 centenarians. In: European Journal of Human Genetics. 2009 ; Vol. 17, No. 11. pp. 1515-1519.
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