Ryu Seungjin, Atzmon Gil, Barzilai Nir, Raghavachari Nalini, Suh Yousin
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Mech Ageing Dev. 2016 Apr;155:7-9. doi: 10.1016/j.mad.2016.02.010. Epub 2016 Feb 27.
Apolipoprotein E (APOE) gene has been the most replicated longevity-associated gene in humans. Two common APOE alleles are either significantly depleted (ε4 allele) or enriched (ε2 allele) in long-lived individuals as compared to controls. We performed high-throughput sequencing analysis of exons and 2kb proximal promoter of APOE in 450 centenarians and 500 controls of Ashkenazi Jewish decent. We found two common regulatory variants, rs405509 (p=0.006) and rs769449 (p=0.036), that were significantly depleted in centenarians. Genotyping analysis of rs7412 and rs429358 showed significant enrichment of ε2 allele (p=0.003) and ε2/ε3 genotype (p=0.005), and significant depletion of ε3/ε4 genotype (p=0.005) in centenarians. Our findings support the hypothesis that variants in both coding and regulatory regions of APOE may contribute to longevity in humans.
载脂蛋白E（APOE）基因是人类中与长寿关联最为密切且被反复验证的基因。与对照组相比，在长寿个体中，两种常见的APOE等位基因要么显著减少（ε4等位基因），要么显著增加（ε2等位基因）。我们对450名百岁老人和500名阿什肯纳兹犹太裔对照者的APOE外显子和2kb近端启动子进行了高通量测序分析。我们发现了两个常见的调控变异体，rs405509（p = 0.006）和rs769449（p = 0.036），在百岁老人中显著减少。rs7412和rs429358的基因分型分析显示，百岁老人中ε2等位基因（p = 0.003）和ε2/ε3基因型（p = 0.005）显著增加，而ε3/ε4基因型（p = 0.005）显著减少。我们的研究结果支持这样的假说，即APOE编码区和调控区的变异可能对人类长寿有贡献。
