No Association between Microsomal Triglyceride Transfer Protein (MTP) Haplotype and Longevity in Humans

Human longevity is a multifactorial condition with a significant genetic contribution. A recent association study in two independent samples of long-lived U.S. Caucasians [long-lived individuals (LLI)] identified a SNP haplotype of the microsomal triglyceride transfer protein (MTP, 4q25) that was un...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-05, Vol.102 (22), p.7906-7909
Main Authors: Nebel, Almut, Peter J. P. Croucher, Stiegeler, Rieke, Nikolaus, Susanna, Krawczak, Michael, Schreiber, Stefan, Kunkel, Louis M.
Format: Article
Language:English
Subjects:
Age
Aged
Aged, 80 and over
Alleles
Biological Sciences
Carrier Proteins - genetics
Genetic Markers - genetics
Genetics
Genetics, Population
Genotype
Genotypes
Germany
Haplotypes
Haplotypes - genetics
Human genetics
Humans
Life expectancy
Longevity
Longevity - genetics
Medical genetics
Population genetics
Proteins
Triglycerides
White people
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Summary:Human longevity is a multifactorial condition with a significant genetic contribution. A recent association study in two independent samples of long-lived U.S. Caucasians [long-lived individuals (LLI)] identified a SNP haplotype of the microsomal triglyceride transfer protein (MTP, 4q25) that was underrepresented among LLI when compared with younger controls. This suggested that variation in the MTP gene might modify human longevity. Because of its function in lipid metabolism, the MTP gene product could plausibly play a pivotal role in the physiology of aging. However, the association observed in the U.S. samples could not be replicated by the same authors in a larger French LLI sample. We have therefore investigated the MTP "risk" haplotype in our own collection of 1,589 German nonagenarians, centenarians, and appropriately matched controls. No statistically significant differences were observed between LLI and controls at the allele, genotype, or haplotype level. This indicates that a noteworthy influence of the respective MTP haplotype on human longevity in the German population is unlikely. Furthermore, in comparison with all other U.S. and European samples analyzed, the MTP "risk" haplotype was found to be overrepresented only in the U.S. controls. This implies that the putative association is more likely to reflect recent changes in the genetic structure of the U.S. Caucasian population as a whole, rather than genetic effects upon survival to old age. In our view, the original study therefore highlights potential problems that arise when the case-control design is used as a means to map longevity genes in humans.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0408670102