Department of Medicine, The Albert Einstein College of Medicine of Yeshiva University, New York, NY, USA.
J Gerontol A Biol Sci Med Sci. 2012 Nov;67(11):1153-60. doi: 10.1093/gerona/gls103. Epub 2012 Apr 10.
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.
单核苷酸多态性 rs2866164 位于 MTP 基因中，与人类长寿有关，但随后的长寿研究并未证实这一点。利用我们的阿什肯纳兹犹太人人群，我们发现与对照组相比，MTP CC 基因型在百岁老人及其后代中明显过多（p<0.05）。然而，当我们随着年龄的增长检查 MTP CC 基因型频率模式时，我们观察到 55-85 岁之间呈单调下降，然后在 90 岁后急剧富集，形成 U 形模式（p<0.05）。此外，MTP CC 基因型受到三种经过验证的长寿基因型的缓冲（p<0.05）。这种缓冲效应使得 MTP CC 基因型在百岁老人中富集，而 CC 对照组中缺乏这种基因型则导致生存能力较差（p<0.05）。因此，我们得出结论，MTP CC 是一种缓冲性有害基因型，评估整个衰老过程中的基因型频率对于从缓冲性有害基因型中识别长寿至关重要。
