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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans
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No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans

机译：微粒体甘油三酸酯转移蛋白（MTP）单倍型与人类寿命之间无关联

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摘要

Human longevity is a multifactorial condition with a significant genetic contribution. A recent association study in two independent samples of long-lived U.S. Caucasians [long-lived individuals (LLI)] identified a SNP haplotype of the microsomal triglyceride transfer protein (MTP, 4q25) that was underrepresented among LLI when compared with younger controls. This suggested that variation in the MTP gene might modify human longevity. Because of its function in lipid metabolism, the MTP gene product could plausibly play a pivotal role in the physiology of aging. However, the association observed in the U.S. samples could not be replicated by the same authors in a larger French LLI sample. We have therefore investigated the MTP "risk" haplotype in our own collection of 1,589 German nonagenarians, centenarians, and appropriately matched controls. No statistically significant differences were observed between LLI and controls at the allele, genotype, or haplotype level. This indicates that a noteworthy influence of the respective MTP haplotype on human longevity in the German population is unlikely. Furthermore, in comparison with all other U.S. and European samples analyzed, the MTP "risk" haplotype was found to be overrepresented only in the U.S. controls. This implies that the putative association is more likely to reflect recent changes in the genetic structure of the U.S. Caucasian population as a whole, rather than genetic effects upon survival to old age. In our view, the original study therefore highlights potential problems that arise when the case-control design is used as a means to map longevity genes in humans.
机译：人类寿命是具有重要遗传贡献的多因素条件。最近一项针对长寿美国高加索人[长寿个体（LLI）]的两个独立样本的关联研究确定了微粒体甘油三酸酯转移蛋白（MTP，4q25）的SNP单倍型，与年轻对照相比，在LLI中代表性不足。这表明MTP基因的变异可能会改变人类的寿命。由于其在脂质代谢中的功能，MTP基因产物可能在衰老的生理过程中起关键作用。但是，在较大的法国LLI样本中，同一作者无法复制在美国样本中观察到的关联。因此，我们在自己的1589名德国非agenarians，百岁老人和适当匹配的控件中收集了MTP的“风险”单倍型。在等位基因，基因型或单倍型水平上，LLI与对照之间未观察到统计学上的显着差异。这表明在德国人口中不太可能出现相应的MTP单倍型对人类寿命的显着影响。此外，与分析的所有其他美国和欧洲样品相比，发现MTP“风险”单倍型仅在美国对照中代表过多。这意味着推定的关联更可能反映出美国白种人整体的遗传结构的最新变化，而不是对老年生存的遗传影响。我们认为，原始研究因此强调了将病例对照设计用作在人类中绘制寿命基因的方法时出现的潜在问题。

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