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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Exome-Wide Association Study Identifies FN3KRP and PGP as New Candidate Longevity Genes
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Exome-Wide Association Study Identifies FN3KRP and PGP as New Candidate Longevity Genes

机译：Exome-Wide的协会研究将FN3KRP和PGP识别为新候选寿命基因

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Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62 488 common and rare coding variants in 1248 German long-lived individuals, including 599 centenarians and 6941 younger controls (age < 60 years). In a single-variant analysis, we observed an exome-wide significant association between rs1046896 in the gene fructosamine-3-kinase-related-protein (FN3KRP) and longevity. Noteworthy, we found the longevity allele C of rs1046896 to be associated with an increased FN3KRP expression in whole blood; a database look-up confirmed this effect for various other human tissues. A gene-based analysis, in which potential cumulative effects of common and rare variants were considered, yielded the gene phosphoglycolate phosphatase (PGP) as another potential longevity gene, though no single variant in PGP reached the discovery p-value (1 x 10E-04). Furthermore, we validated the previously reported longevity locus cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1). Replication of our results in a French longevity cohort was only successful for rs1063192 in CDKN2B-AS1. In conclusion, we identified 2 new potential candidate longevity genes, FN3KRP and PGP which may influence the phenotype through their role in metabolic processes, that is, the reverse glycation of proteins (FN3KRP) and the control of glycerol-3-phosphate levels (PGP).
机译：尽管做出了巨大的研究努力，但长寿的基因组成在很大程度上仍然难以捉摸。对主要位于内含子或调控区的常见变异的研究，在表型遗传力方面只获得了很少的新信息。在此，我们进行了一项基于芯片的全外显子组关联研究，调查了1248名德国长寿人群中的62 488种常见和罕见编码变体，其中包括599名百岁老人和6941名年轻对照（年龄<60岁）。在一项单变量分析中，我们观察到果糖胺-3-激酶相关蛋白（FN3KRP）基因中的rs1046896与寿命之间存在外显子组范围的显著关联。值得注意的是，我们发现rs1046896的长寿等位基因C与全血中FN3KRP表达增加有关；数据库查询证实了其他各种人体组织的这种效应。一项基于基因的分析（其中考虑了常见和罕见变异的潜在累积效应）得出了另一个潜在长寿基因磷酸甘醇磷酸酶（PGP），尽管PGP中没有任何单一变异达到发现p值（1 x 10E-04）。此外，我们验证了之前报道的长寿基因座细胞周期蛋白依赖性激酶抑制剂2B反义RNA 1（CDKN2B-AS1）。我们在法国长寿队列中复制的结果仅在CDKN2B-AS1中的rs1063192中成功。总之，我们发现了两个新的潜在候选长寿基因FN3KRP和PGP，它们可能通过在代谢过程中的作用影响表型，即蛋白质的反糖基化（FN3KRP）和甘油-3-磷酸水平的控制（PGP）。

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