Research press release





今回、Benjamin Sun、Adam Butterworthたちの研究グループは、標的分子と特異的に結合する短いDNA鎖(アプタマー)を調べて、3301人の健常者の血漿に含まれる3622のタンパク質を定量した。試料は、INTERVALという英国の研究において採取されたものが用いられた。INTERVALとは、約5万人が献血者として参加し、献血から次の献血までの間隔を最適にして英国の国民保健サービスの輸血用血液を改善することを目的として行われた研究だ。今回の研究では、ゲノム領域と1478のタンパク質の間に1927の関連が同定され、そのうちの89%が今回初めて同定されたものだった。また、これらの部位と遺伝子発現調節領域の間にかなりのオーバーラップがあり、常にではないが、多くの場合に、タンパク質の量が遺伝子発現量によって決まることが示唆された。


A genetic atlas of the human plasma proteome is reported in a paper published in this week’s Nature. The associations identified by this study between genetic variation and the levels of individual proteins may suggest new therapeutic targets and avenues to apply existing drugs to new diseases.

Blood plasma proteins are vital to various biological processes, including growth, repair, signalling, transport and fighting infection. They are important drug targets, and are frequently differentially regulated during disease. However, relatively little is known about the genetic factors that determine an individual’s plasma protein levels, with previous studies having been limited in scope.

Benjamin Sun, Adam Butterworth and colleagues studied short DNA strands that bind to specific target molecules - aptamers - to quantify 3,622 proteins in the blood plasma of 3,301 healthy individuals. Samples were taken from INTERVAL, a study of nearly 50,000 UK blood donors intended to improve NHS blood supplies by identifying the optimum interval between blood donations. The team identify 1,927 associations between regions of the genome and 1,478 proteins - 89% of which were previously unidentified. There is considerable overlap between these locations and regions that regulate gene expression, suggesting that protein levels are often, but not always, determined by levels of gene production.

In addition, the authors identify links between particular genetic variations from their study with previously identified regions that are associated with common diseases. Understanding the relationship between diseases, genetic variation and the levels of particular proteins could pave the way for the identification of new therapeutic target proteins and new ways of employing existing drugs, as well as aid in the determination of potential risks for medicines currently under development.

doi: 10.1038/s41586-018-0175-2

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