Distinguishing Between Longevity and Buffered-Deleterious Genotypes for Exceptional Human Longevity: The Case of the MTP Gene
Distinguishing Between Longevity and Buffered-Deleterious Genotypes for Exceptional Human Longevity: The Case of the MTP Gene
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DOI：
10.1093/gerona/gls103
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发表时间：
2012-11-01
影响因子：
5.1
通讯作者：
Atzmon, Gil
中科院分区：
文献类型：
--
作者：
Huffman, Derek M.;Deelen, Joris;Atzmon, Gil
MTP基因中的单核苷酸多态性rs2866164已与人类长寿相关，但尚未得到后续长寿研究的验证。利用我们的德系犹太人群体，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显着过高 (p < .05)。然而，当我们检查 MTP CC 基因型频率模式随衰老的变化时，我们观察到 55-85 岁之间单调下降，随后在 90 岁后急剧丰富，形成 U 形模式 (p < .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 < .05)。人们发现，这种缓冲效应使百岁老人的 MTP CC 基因型富集，而 CC 对照中缺乏 MTP CC 基因型，导致生存率较差 (p < .05)。因此，我们得出结论，MTP CC 是一种缓冲有害基因型，评估整个衰老过程中的基因型频率对于辨别缓冲有害基因型的寿命至关重要。
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.