ティチン機能喪失変種と早期発症の心房細動との関連

Seung Hoan Choi¹, Lu-Chen Weng^1,2, Carolina Roselli¹

¹Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

JAMA

|December 12, 2018

まとめ

TTN遺伝子の遺伝的変異は,早発性心房細動 (AF) と関連しています. TTNにおける機能喪失の変異は早期発症したAFの個体においてより頻繁に発見され,潜在的な遺伝的関連性を示唆した.

科学分野:

遺伝学
心臓病科
ゲノミクス

背景:

心房細動 (AF) は,特に遺伝的要因が重要な役割を果たす若い個体において,一般的な心律乱です.
早期発症したAFの根底にある正確な遺伝的メカニズムは,まだ完全に理解されていないため,さらなる調査が必要である.

研究の目的:

大規模な全ゲノム配列解析を行い,心房細動 (AF) に関連する遺伝的変異を特定する.
機能喪失 (LOF) 変種と早期発症のAFとの関連を調査する.

主な方法:

症例対照研究では,トランスオミクス・フォー・プレシジョン・メディシン・プログラム内の18,526人の全ゲノムシーケンシングデータを利用した.
早期発症したAF患者2,781人を,ヨーロッパ出身の対照群4,959人と比較した.
結果は英国バイオバンクとマイコード研究で検証された.

主要な成果:

サルコメリックタンパク質チチンをコードするTTN遺伝子の機能喪失 (LOF) 変異は,早期発症したAF症例の2. 1%と対照群の1. 1%で確認された (OR,1. 76).
TTN LOFの多様性の存在は,AFの発症の早い年齢とともに,特に30歳以前に発症した患者で増加した (OR,5. 94).
この関連は独立したコホートで再現され,TTN LOF変種と早期発症のAFとの関連が確認されました.

結論:

TTN遺伝子の機能喪失変異と早発性心房細動の間に統計的に有意な関連性がある.
早期発症したAF症例の少数はTTN LOFの変異体であったが,因果関係を確立するにはさらなる研究が必要である.

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