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妊娠高血圧腎症の母児のDNAサンプルを用いた長鎖型シークエンサーによるHLA-Gゲノム配列の解析

西澤 絢子 東北大学

2021.03.25

概要

妊娠高血圧腎症は、高血圧およびタンパク尿を主徴とする重篤な周産期疾患であり、母体胎児合併症や死亡の主要な原因である。HLA(human leukocyte antigen)-Gは,母体と胎児の免疫寛容に重要な役割を果たしていると考えられており、HLA-G 遺伝子多型と周産期疾患の発症との関連が広範に検討されてきた。近年まで同遺伝子領域の詳細な配列解析は困難であったため、HLA-G 遺伝子型と妊娠高血圧腎症の発症との関連性については、いまだ結論が出ていない。本研究では、長鎖型シークエンサーである PacBio RSII プラットフォームを用いて、31 組の母児のゲノム DNA サンプル(正常妊娠・出産 18 組、妊娠高血圧腎症 13 組)から HLA-G 領域のゲノム配列 (5.2 kb)を 1 分子リアルタイムシークエンシングで取得した。同定された HLA-G 対立遺伝子は既知の 7 つの HLA-G 対立遺伝子とおおむね一致した。公開データベース上の HLA-G 遺伝子領域、3.1 kb のヌクレオチド配列と比較して HLA-G のアレルにおいて第 2 区域(アミノ酸の変異を伴う多型)で 1 本、第 4 区域(イントロンなど、アミノ酸の変異を伴わない多型)で 1 本、計 2 本の新規 HLA-G 対立遺伝子を同定した。さらに、妊娠高血圧腎症の発症と HLA-G*01:01:01:01 対立遺伝子の下流領域内に存在する T ストレッチ(チミンの繰り返し:本研究では 17~43 bp)との間に関連性を見出した。

本研究は、HLA-G の長鎖型シークエンシングが、妊娠高血圧腎症の病態生理に関与する HLA-G バリアントの特徴を明らかにする可能性を初めて示唆した。

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