Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity

The case of the MTP gene

Derek M. Huffman, Joris Deelen, Qian K. Ye, Aviv Bergman, Eline P. Slagboom, Nir Barzilai, Gil Atzmon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.

Original languageEnglish (US)
Pages (from-to)1153-1160
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume67
Issue number11
DOIs
StatePublished - Nov 2012

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Genotype
Genes
Jews
Single Nucleotide Polymorphism
Survival Rate
Population

Keywords

  • Aging
  • Buffering mechanism
  • Genetics
  • Microsomal triglyceride transfer protein

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

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abstract = "The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.",
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AU - Ye, Qian K.

AU - Bergman, Aviv

AU - Slagboom, Eline P.

AU - Barzilai, Nir

AU - Atzmon, Gil

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N2 - The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.

AB - The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.

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