TY - JOUR
T1 - Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity
T2 - The case of the MTP gene
AU - Huffman, Derek M.
AU - Deelen, Joris
AU - Ye, Kenny
AU - Bergman, Aviv
AU - Slagboom, Eline P.
AU - Barzilai, Nir
AU - Atzmon, Gil
N1 - Funding Information:
This work has been supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, the General Clinical Research Center ( M01-RR12248 ), and the Diabetes Research and Training Center ( DK20541 ) at the Albert Einstein College of Medicine and grants AG027734, AG028872 , RR12248 , and M01RR12248 from the National Institutes of Health . D.M.H. is supported by an National Institute of Aging -sponsored K99 award (AG037574).
PY - 2012/11
Y1 - 2012/11
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.
KW - Aging
KW - Buffering mechanism
KW - Genetics
KW - Microsomal triglyceride transfer protein
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U2 - 10.1093/gerona/gls103
DO - 10.1093/gerona/gls103
M3 - Article
C2 - 22496539
AN - SCOPUS:84867487903
SN - 1079-5006
VL - 67
SP - 1153
EP - 1160
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 11
ER -