Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan

Bard J. Geesaman, Erica Benson, Stephanie J. Brewster, Louis M. Kunkel, Hélène Blanché, Gilles Thomas, Thomas T. Perls, Mark J. Daly, Annibale A. Puca

Research output: Contribution to journalArticlepeer-review

Abstract

We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains ≈50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy-Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity.

Original languageEnglish
Pages (from-to)14115-14120
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue numberSUPPL. 2
DOIs
Publication statusPublished - Nov 25 2003

ASJC Scopus subject areas

  • Genetics
  • General

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